黄芪多糖辅助抗癌作用的机制研究
|
摘要
目的：探讨黄芪多糖(Astragalus polysaccharide APS)体内外是否具有化疗增敏作用及其可能机制。
方法：荷H22小鼠肝癌细胞株皮下移植瘤小鼠经腹腔给以APS及ADM,观察其体内对移植瘤生长的影响及对昆明小鼠主要脏器的毒性。用ELISA方法检测血清中IL-1a、IL-2、IL-6、TNF-α、IL-10等细胞因子的表达；用Western blot和荧光定量PCR检测肿瘤组织中的P-GP和MDR1mRNA表达。体外用MTT法检测APS单独和协同化疗药对H22/ADM敏感性；用Western blot和荧光定量PCR检测H22/ADM耐药细胞株的P-GP和MDR1mRNA表达；用R-123摄取实验研究不同浓度APS对H22/ADM细胞P-GP功能的影响。
结果：各实验组KM小鼠皮下接种部位成瘤率100%,荷H22小鼠肝癌细胞株皮下移植瘤模型成功；体内实验表明,在剂量50mg/kg～200mg/kg范围内APS能减轻ADM所导致的KM小鼠体重下降,但对肝、心、肾、肺重量及其脏器系数无明显影响。在剂量100mg/kg～200mg/kg范围内APS能减轻由AMD导致的胸腺减小,在剂量50mg/kg～200mg/kg范围内APS能减轻由AMD导致的脾脏减小。在剂量50mg/kg～200mg/kg范围内APS联用ADM对荷瘤小鼠肿瘤生长有较强的抑制作用；在剂量50mg/kg～200mg/kg范围内,含APS组IL-1a、IL-2、IL-6、TNF-α等因子表达增加,而IL-10因子表达减少,与ADM组比较均有显著性差异(P<0.05),APS具有辅助ADM抗肿瘤作用机制之一可能与APS增加IL-1a、IL-2、IL-6、TNF-α等因子表达,而减少IL-10因子产生有关；在APS剂量50mg/kg～200mg/kg范围内MDR1mRNA和P-GP的表达随着APS剂量增加而减小,呈浓度依赖性。与ADM或ADM+RFP组比较,ADM+APS (200mg/kg)组MDR1mRNA和P-GP的表达明显减小(P<0.05)。APS能下调MDR1mRNA水平,减少P-GP表达,因此可能增加化疗药物在肿瘤细胞内的浓度,这也许是APS增强ADM的化疗敏感性,辅助ADM抗肿瘤作用的另一机制。体外研究发现,在终浓度0.8-500mg/mL范围,APS对H22/ADM耐药细胞株无抗肿瘤作用,但可增强5-Fu、 DDP、VP-16或CTX等常用化疗药物对H22/ADM耐药细胞株的化疗敏感性；APS可以使R-123潴留增加,对P-GP外排功能表现为抑制作用；APS下调MDR1mRNA作用随APS浓度增加而作用增强,呈浓度依赖性,APS各组MDR1mRNA表达随干预时间的延长而减少,均具有时间依赖性；在同一时间内,APS下调P-GP表达随APS浓度增加而增强,呈浓度依赖性,同一浓度的APS下调P-GP表达随干预时间的延长而增强(72h>48h>24h),呈时间依赖性。对于H22/ADM耐药细胞株,APS下调MDR1mRNA和P-GP的表达,抑制P-GP外排功能可能是APS增强耐药细胞株H22/ADM的化疗敏感性的机制之一。
结论：APS具有辅助抗肿瘤作用,其机制可能与APS增加IL-1a、 IL-2、IL-6、TNF-α等因子表达,而减少IL-10因子产生,以及降低P-GP外排功能,下调P-GP和MDR1mRNA表达有关。
Objective:To investigate the adjunct anticancer role of Astragalus polysaccharides in H22tumor-bearing mice and H22/ADM cell lines.
Methods:H22tumor-bearing mice were treated by APS and ADM intraperitoneally, after ten days of treatment, blood samples were collected from mouse eyes and serum was harvested by centrifugation. Mice were sacrificed, and the whole body, tumor, spleen, and thymus were weighed immediately. The rate of tumor inhibition and organ indexes were calculated. The expression levels of cytokines in sera and the expression levels of P-glycoprotein (P-GP) and multidrug resistance (MDR)1mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay, Western blotting, and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction, respectively. H22/ADM cell lines were treated with different concentrations of APS and/or the most common chemotherapy drugs, such as Cyclophosphamid, Adriamycin,5-Fluorouracil, Cisplatin, Etoposide, and Vincristine. Chemotherapeutic drug sensitivity, P-glycoprotein function and expression, and MDR1mRNA expression were detected using MTT assay, flow cytometry, Western blotting, and quantitative RT-PCR.
Results:The tumor inhibition rates in the treatment groups: Adriamycin (ADM)+Astragalus polysaccharides (APS)(50mg/kg), ADM+APS (100mg/kg), and ADM+APS (200mg/kg) were significantly higher than in the ADM group. The spleen indexes of the above groups were also significantly higher than in the ADM group, and the thymus indexes of the ADM+APS (100mg/kg), ADM+APS (200mg/kg) groups were significantly higher than in the ADM group. APS was found to exert a synergistic anti-tumor effect with Adriamycin and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD. The expression of interleukin-1alpha (IL-la), interleukin-2(IL-2), interleukin-6(IL-6), and tumor necrosis factor-a (TNF-a) were significantly higher in the ADM+APS (50mg/kg), ADM+APS (100mg/kg) and ADM+APS (200mg/kg) groups than in the ADM group; and interleukin-10(IL-10) was significantly lower in the above groups than in the ADM group. Results show that APS could increase IL-la, IL-2, IL-6, and TNF-a expression and decrease IL-10levels. Compared to the ADM group, APS treatment at a dose concentration of50-200mg/kg could down regulate MDRl mRNA expression in a concentration-dependent manner. The expression level of P-GP was significantly lower in the ADM+APS (200mg/kg) group than in the ADM group.
When used alone, APS had no anti-tumor activity in H22/ADM cells in vitro. However, it can increase the cytotoxicity of certain chemotherapy drugs, such as Cyclophosphamid, Adriamycin,5-Fluorouracil, Cisplatin, Etoposide, and Vincristine, in H22/ADM cells. It acts in a dose-dependent manner. Compared to a blank control group, APS increased intracellular Rhodamine-123retention and decreased P-glycoprotein efflux function in a dose-dependent manner. These factors were assessed24h,48h, and72h after administration. APS down regulated P-glycoprotein and MDR1mRNA expression in a concentration-dependent manner within a final range of0.8-500mg/L and in a time-dependent manner from24-72h.
Conclusion:The adjunct anticancer mechanism of astragalus polysaccharide in vivo and in vitro may be related to its ability to increase expression of IL-la, IL-2, IL-6, and TNF-a, decrease IL-10, and down regulate MDR1mRNA and P-GP expression levels.
方法：荷H22小鼠肝癌细胞株皮下移植瘤小鼠经腹腔给以APS及ADM,观察其体内对移植瘤生长的影响及对昆明小鼠主要脏器的毒性。用ELISA方法检测血清中IL-1a、IL-2、IL-6、TNF-α、IL-10等细胞因子的表达；用Western blot和荧光定量PCR检测肿瘤组织中的P-GP和MDR1mRNA表达。体外用MTT法检测APS单独和协同化疗药对H22/ADM敏感性；用Western blot和荧光定量PCR检测H22/ADM耐药细胞株的P-GP和MDR1mRNA表达；用R-123摄取实验研究不同浓度APS对H22/ADM细胞P-GP功能的影响。
结果：各实验组KM小鼠皮下接种部位成瘤率100%,荷H22小鼠肝癌细胞株皮下移植瘤模型成功；体内实验表明,在剂量50mg/kg～200mg/kg范围内APS能减轻ADM所导致的KM小鼠体重下降,但对肝、心、肾、肺重量及其脏器系数无明显影响。在剂量100mg/kg～200mg/kg范围内APS能减轻由AMD导致的胸腺减小,在剂量50mg/kg～200mg/kg范围内APS能减轻由AMD导致的脾脏减小。在剂量50mg/kg～200mg/kg范围内APS联用ADM对荷瘤小鼠肿瘤生长有较强的抑制作用；在剂量50mg/kg～200mg/kg范围内,含APS组IL-1a、IL-2、IL-6、TNF-α等因子表达增加,而IL-10因子表达减少,与ADM组比较均有显著性差异(P<0.05),APS具有辅助ADM抗肿瘤作用机制之一可能与APS增加IL-1a、IL-2、IL-6、TNF-α等因子表达,而减少IL-10因子产生有关；在APS剂量50mg/kg～200mg/kg范围内MDR1mRNA和P-GP的表达随着APS剂量增加而减小,呈浓度依赖性。与ADM或ADM+RFP组比较,ADM+APS (200mg/kg)组MDR1mRNA和P-GP的表达明显减小(P<0.05)。APS能下调MDR1mRNA水平,减少P-GP表达,因此可能增加化疗药物在肿瘤细胞内的浓度,这也许是APS增强ADM的化疗敏感性,辅助ADM抗肿瘤作用的另一机制。体外研究发现,在终浓度0.8-500mg/mL范围,APS对H22/ADM耐药细胞株无抗肿瘤作用,但可增强5-Fu、 DDP、VP-16或CTX等常用化疗药物对H22/ADM耐药细胞株的化疗敏感性；APS可以使R-123潴留增加,对P-GP外排功能表现为抑制作用；APS下调MDR1mRNA作用随APS浓度增加而作用增强,呈浓度依赖性,APS各组MDR1mRNA表达随干预时间的延长而减少,均具有时间依赖性；在同一时间内,APS下调P-GP表达随APS浓度增加而增强,呈浓度依赖性,同一浓度的APS下调P-GP表达随干预时间的延长而增强(72h>48h>24h),呈时间依赖性。对于H22/ADM耐药细胞株,APS下调MDR1mRNA和P-GP的表达,抑制P-GP外排功能可能是APS增强耐药细胞株H22/ADM的化疗敏感性的机制之一。
结论：APS具有辅助抗肿瘤作用,其机制可能与APS增加IL-1a、 IL-2、IL-6、TNF-α等因子表达,而减少IL-10因子产生,以及降低P-GP外排功能,下调P-GP和MDR1mRNA表达有关。
Objective:To investigate the adjunct anticancer role of Astragalus polysaccharides in H22tumor-bearing mice and H22/ADM cell lines.
Methods:H22tumor-bearing mice were treated by APS and ADM intraperitoneally, after ten days of treatment, blood samples were collected from mouse eyes and serum was harvested by centrifugation. Mice were sacrificed, and the whole body, tumor, spleen, and thymus were weighed immediately. The rate of tumor inhibition and organ indexes were calculated. The expression levels of cytokines in sera and the expression levels of P-glycoprotein (P-GP) and multidrug resistance (MDR)1mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay, Western blotting, and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction, respectively. H22/ADM cell lines were treated with different concentrations of APS and/or the most common chemotherapy drugs, such as Cyclophosphamid, Adriamycin,5-Fluorouracil, Cisplatin, Etoposide, and Vincristine. Chemotherapeutic drug sensitivity, P-glycoprotein function and expression, and MDR1mRNA expression were detected using MTT assay, flow cytometry, Western blotting, and quantitative RT-PCR.
Results:The tumor inhibition rates in the treatment groups: Adriamycin (ADM)+Astragalus polysaccharides (APS)(50mg/kg), ADM+APS (100mg/kg), and ADM+APS (200mg/kg) were significantly higher than in the ADM group. The spleen indexes of the above groups were also significantly higher than in the ADM group, and the thymus indexes of the ADM+APS (100mg/kg), ADM+APS (200mg/kg) groups were significantly higher than in the ADM group. APS was found to exert a synergistic anti-tumor effect with Adriamycin and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD. The expression of interleukin-1alpha (IL-la), interleukin-2(IL-2), interleukin-6(IL-6), and tumor necrosis factor-a (TNF-a) were significantly higher in the ADM+APS (50mg/kg), ADM+APS (100mg/kg) and ADM+APS (200mg/kg) groups than in the ADM group; and interleukin-10(IL-10) was significantly lower in the above groups than in the ADM group. Results show that APS could increase IL-la, IL-2, IL-6, and TNF-a expression and decrease IL-10levels. Compared to the ADM group, APS treatment at a dose concentration of50-200mg/kg could down regulate MDRl mRNA expression in a concentration-dependent manner. The expression level of P-GP was significantly lower in the ADM+APS (200mg/kg) group than in the ADM group.
When used alone, APS had no anti-tumor activity in H22/ADM cells in vitro. However, it can increase the cytotoxicity of certain chemotherapy drugs, such as Cyclophosphamid, Adriamycin,5-Fluorouracil, Cisplatin, Etoposide, and Vincristine, in H22/ADM cells. It acts in a dose-dependent manner. Compared to a blank control group, APS increased intracellular Rhodamine-123retention and decreased P-glycoprotein efflux function in a dose-dependent manner. These factors were assessed24h,48h, and72h after administration. APS down regulated P-glycoprotein and MDR1mRNA expression in a concentration-dependent manner within a final range of0.8-500mg/L and in a time-dependent manner from24-72h.
Conclusion:The adjunct anticancer mechanism of astragalus polysaccharide in vivo and in vitro may be related to its ability to increase expression of IL-la, IL-2, IL-6, and TNF-a, decrease IL-10, and down regulate MDR1mRNA and P-GP expression levels.
引文
[1]Freddie Bray, Ahmedin Jemal, Nathan Grey, Jacques Ferlay, David Forman. Global cancer transitions according to the Human Development Index (2008-2030):a population-based study. The Lancet Oncology 2012,13(8): 790-801. doi:10.1016/S1470-2045(12)70211-5.
[2]Urruticoechea A, Alemany R, Balart J, Villanueva A, Vinals F, Capella G:Recent advances in cancer therapy:an overview. Curr Pharm Des 2010,16(1):3-10.
[3]Kellof GJ:Perspective on cancer chemoprevention research and drug development. Adv Cancer Res 2000,78:199-334.
[4]Choi CH:ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell Int 2005,5:30.
[5]Wong R, Sagar CM, Sagar SM:Integration of Chinese medicine into supportive cancer care:A modern role for an ancient tradition. Cancer Treat Rev 2001, 27(4):235-246.
[6]Ebinger M, Uhr M. ABC drug transporter at the blood-brain barrier:effects on drug metabolism and drug response[J]. Eur Arch Psychiatry Clin Neurosci,2006, 256(5):294-298,
[7]Fromm MF. Importance of P-glycoprotein at blood-tissue barriers[J]. Trends Pharmacol Sci,2004,25(8):423-429.
[8]Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants[J]. Biochim Biophys Acta,1976, 455(1):152-162.
[9]Demeule M, Regina A, Jodoin J, et al. Drug transport to the brain:key roles for the efflux pump P-glycoprotein in the blood-brain barrier[J]. Vascul Pharmacol, 2002,38(6):339-348.
[10]Schinkel AH, Jonker JW. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family:an overview[J]. Adv Drug Deliv Rev,2003,55(1):3-29.
[11]李睿,海帆.多药耐药蛋白P-糖蛋白的研究进展[J].中国实用医药,2009,4(2)：240-242.
[12]Teda Y, Wada M, Migita T, el al. Increased expression of multi-drug resistance-associated proteins in bladder cancer during clinical course and drug resistance to doxorubicin[J]. Int J Cancer,2002,98:630-635.
[13]Qi F, Li A, Inagaki Y, Gao J, Li J, Kokudo N, Li XK, Tang W:Chinese herbal medicines as adjuvant treatment during chemo-or radio-therapy for cancer. Biosci Trends 2010,4(6):297-307.
[14]Ruan WJ, Lai MD, Zhou JG:Anticancer effects of Chinese herbal medicine, science or myth? J Zhejiang Univ Sci B 2006,7(12):1006-1014.
[15]Konkimalla VB, Efferth T:Evidence-based Chinese medicine for cancer therapy. J Ethnopharmacol.2008,116(2):207-210.
[16]Ji DB, Ye J, Jiang YM, Qian BW:Anti-tumor effect of Liqi, a traditional Chinese medicine prescription, in tumor bearing mice. BMC Complement Altern Med 2009,9:20.
[17]胡军,金伟,杨佩满.p-榄香烯逆转人乳腺癌MCF-7/ADM细胞对阿霉素耐药性的研究[J].中华肿瘤杂志,2004,26(2)：268-270.
[18]沈朋,夏蕾,张海江.逆转肿瘤细胞多药耐药性的四物合剂有效组分[J].中国中药杂志,2005,30(7)：520.
[19]吕淑华。 黄芪多糖抗肿瘤作用研究进展[J].江西中医学院学报,2009,21(1)：85-87.
[20]Balch PA:Prescription for Nutritional Healing, A Practical A-to-Z Reference to Drug-Free Remedies Using Vitamins, Minerals, Herbs and Food Supplements. Fifth Edition, Avery Penguin Putnam Inc., New York, NY, USA,2006.
[21]Rittenhouse JR, Lui PD, Lau BH:Chinese medicinal herbs reverse macrophage suppression induced by urological tumors. J Urol 1991,146(2):486-490.
[22]Ma XQ, Shi Q, Duan JA, Dong TT, Tsim KW:Chemical analysis of Radix Astragali(Huangqi) in China:a comparison with its adulterants and seasonal variations. J Agric Food Chem 2002,50(17):4861-4866.
[23]Shao BM, Xu W, Dai H, Tu P, Li Z, Gao XM:A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb. Biochem Biophys Res Commun 2004,320 (4):1103-1111.
[24]Li J, Bao Y, Lam W, Li W, Lu F, Zhu X, Liu J, Wang H:Immunoregulatory and anti-tumor effects of polysaccharopeptide and Astragalus polysaccharides on tumor-bearing mice. Immunopharmacol Immunotoxicol 2008,30(4):771-782.
[25]Liu X, Yang Y, Zhang X, Xu S, He S, Huang W, Roberts MS:Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta/Smad in HepG2 cell. J Gastroenterol Hepatol 2010,25(2):420-426.
[26]Zhao LH, Ma ZX, Zhu J, Yu XH, Weng DP:Characterization of polysaccharide from Astragalus radix as the macrophage stimulator. Cell Immunol 2011, 271(2):329-334.
[27]World Health Organization (WHO). Medicinal Plants in China. Manila:WHO Regional Publications,1989.
[28]Zee-Cheng RK:Shi-quan-da-bu-tang (ten signifcant tonic decoction), SQT. A potent Chinese biological response modifier in cancer immunotherapy, potentiation and detoxification of anticancer drugs. Methods Find Exp Clin Pharmacol 1992,14(9):725-736.
[29]Cui R, He J, Wang B, Zhang F, Chen G, Yin S, Shen H:Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats. Cancer Chemother Pharmacol 2003,51(1):75-80.
[30]Wang J, Ito H, Shimura K:Enhancing effect of antitumor polysaccharide from Astragalus or Radix hedysarum on C3 cleavage production of macrophages in mice. Jpn J Pharmacol 1989,51 (3):432-434.
[31]Guo L, Bai SP, Zhao L, Wang XH:Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer:effects on quality of life and survival. Med Oncol 2011 Sep 18.
[32]Liu XN, Zhang CY, Jin XD, Li YZ, Zheng XZ, Li L:Inhibitory effect of schisandrin B on gastric cancer cells in vitro. World J Gastroenterol 2007, 13(48):6506-6511.
[33]Zhang G, Shi L, Selke M, Wang X:CdTe quantum dots with daunorubicin induce apoptosis of multidrug-resistant human hepatoma HepG2/ADM cells:in vitro and in vivo evaluation. Nanoscale Res Lett 2011,6(1):418.
[34]Collett A, Tanianis-Hughes J, Warhurst G:Rapid induction of P-glycoprotein expression by high permeability compounds in colonic cells in vitro:a possible source of transporter mediated drug interactions? Biochem Pharmacol 2004,68(4): 783-790.
[35]Mi Y, Lou L:ZD6474 reverses multidrug resistance by directly inhibiting the function of P-glycoprotein. Br J Cancer 2007,97(7):934-940.
[36]Liu XN, Zhang CY, Jin XD, Li YZ, Zheng XZ, Li L. Inhibitory effect of schisandrin B on gastric cancer cells in vitro. World J Gastroenterol,2007; 13(48):6506-6511. PMID:18161920
[37]Xiaoguang C, Hongyan L, Xiaohong L, Zhaodi F, Yan L, Lihua T, Rui H. Cancer chemopreventive and therapeutic activities of red ginseng. Journal of Ethnopharmacology,1998; 60(1):71-78. doi:10.1016/S0378-8741(97)00133-5 PMID:9533434
[38]Gao L, Chen L, Fei XH, Qiu HY, Zhou H, Wang JM. STI571 combined with vincristine greatly suppressed the tumor formation of multidrug-resistant K562 cells in a human-nude mice xenograft model. Chinese Medical Journal (English), 2006; 119(11):911-918. PMID:16780770
[39]王硕,苏杭,袁经权,等。实验小鼠在癌症研究中的应用及其进展[J],中国比较医学杂志,2011,21(9)：63-67.
[40]万继英,韩庶勇.肿瘤实验动物模型的建立及应用研究进展[J].医学综述,2009,15(19)：2959-2961.
[41]施新猷,王四旺,顾为望,等。比较医学[M]。第1版。西安：陕西科学技术出版社,2003,478-480.
[42]中华人民共和国卫生部药政局。 新药(西药)临床前研究指导原则汇编[M]。北京：人民卫生出版社出版,1993,137-139.
[43]刘一, 边原,叶云,等。 阿霉素抗肿瘤作用的研究进展[J].卢州医学院学报,2008,31(1)：101-103.
[44]Xu JH, Deng WL, Fan ZZ:Effects of changwelqing on nuclear translocation of Y-box binding protein-1 and expregslon of P-glycoprotein in human colon cancer cell line with drug-resistance induced by vincristine. Zhongguo Zhong Xi Yi Jie He Za Zhi.2010,30(7):743-747.
[45]An HJ, Wang XY, Yu M, Sheng J, Li PT, Zhang B:Influence of preventing formula for UC on P-gp level in colon tissue of ulcerative colitis in rats. Journal of TCM Univ. of Hunan 2009,29(4):15-17.
[46]Huang CH, Xie ZX, Qin Q:The mechanism of Chinese medicine compound jiexinkang to reverse the multidrug resistance of K562/A02 cells. Journal of TCM Univ. of Hunan 2004,24(1):7-10.
[47]Zhou RF, Liu PX, Tan M:Effect of Astragalus mongholicus injection on proliferation and apoptosis of hormone sensitive (MCF-7) breast cancer cell lines with physiological dose E2. Zhong Yao Cai.2009,32(5):744-747.
[48]Li Q, Bao JM, Li XL, Zhang T, Shen XH:Inhibiting effect of Astragalus polysaccharides on the functions of CD4+CD25 highTreg cells in the tumor microenvironment of human hepatocellular carcinoma. Chin Med J (Engl).2012, 125(5):786-793.
[49]孙曼霁,周廷冲。中国药物研究与发展[M]。第1版。北京：科学出版社, 1996,63-83。
[50]穆玉兰,汤春生,刘鸣,等。实验性持续腹腔化疗裸小鼠人卵巢癌腹腔移植瘤[J]。山东医科大学学报,2000,38(1)：278-280。
[51]赵莲华,李清,林梵,等.黄芪多糖协同顾铂对Bel-7404人肝癌细胞的杀伤作用[J].实用癌症杂志,2005,20(1)：34-35.
[52]谷俊朝,余微波,王字,等.黄芪多糖对TA2小鼠乳腺癌MA-891移植瘤生长及HSP70表达的影响[J].中华肿瘤防治杂志,2006,13(20)：1534-1537.
[53]黄宏思,黄卫彤,韦鹏涯,等.黄芪多糖联合顺铂治疗H22肝癌的实验研究[J].广西医科大学学报,2009,26(1)：19-21.
[54]章志翔,戚峰,周德俊,等.氟尿嘧啶联合黄芪对小鼠胃癌组织氨基酸代谢的影响[J].中华胃肠外科杂志,2006,9(5)：445.
[55]韩子敏,王巧风,高福音,等.黄芪川芎嗪注射液加化疗治疗恶性肿瘤36例[J].第四军医大学学报,2006,27(13)：1207.
[56]黄金明。黄芪对S180荷瘤小鼠的免疫增强及抑瘤作用[J].中国临床免疫学杂志,1995,7(1)：41
[57]张威. 黄芪多糖的免疫促进作用.科学通报,1979,16：764.
[58]赵克胜,丁丽轩,孔海微,等. 黄芪多糖增强人外周血单核细胞产生肿瘤坏死因子的研究[J].中国中西医结合杂志,1993,13(5)：263.
[59]杨巧,庄英帜。肿瘤多药耐药治疗策略：P-qp抑制剂研究进展[J]。海南医学,2011,6：112-115.
[60]Haus-Cohen M, Assaraf YG, Binyamin L, et al. Disruption of P-glycoprotein anticancer drug efflux activity by a small recombinant single-chain Fv antibody fragment targeted to an extracellular epitope[J]. Int J Cancer.2004, 109(5):750-758.
[61]刘嘉,曾庆琪。中药活性成分逆转肿瘤多药耐药的研究进展[J],中医药信息,2011,28(5),112-114.
[62]杨慧莹,赵丽,郭青龙。P-糖蛋白抑制剂的研究进展[J]。实用老年医学,2011,25(2)： 165-169.
[63]柳林,李红,刘欣。中药逆转恶性肿瘤多药耐药的研究进展[J]。山东医药,2008,48(39)：116-117.
[64]Dizdarevic S, Peters AM. Imaging of multidrug resistance in cancer. Cancer Imaging 2011; 11:1-8 [PMID:21362586 DOI:10.1102/1470-7330.2011.0001]
[65]Goda K, Bacso Z, Szabo G. Multidrug resistance through the spectacle of P-glycoprotein. Curr Cancer Drug Targets 2009; 9:281-297 [PMID:19442049 DOI:10.2174/156800909788166493]
[66]Mayur YC, Peters GJ, Prasad VV, Lemo C, Sathish NK. Design of new drug molecules to be used in reversing multidrug resistance in cancer cells. Curr Cancer Drug Targets 2009; 9:298-306 [PMID:19442050 DOI: 10.2174/156800909788166619]
[67]闻镍,张双庆,朱凌,等。P-糖蛋白最新研究进展。中国药事[J],2011,25(7)：718-723.
[68]刘艳.P-糖蛋白与肿瘤多药耐药[J].海南医学,2010,21(1)：117-119.
[69]李峥,庄笑梅,李素云,等.P-糖蛋白中药抑制剂的研究进展[J].2009,25(4)：326-329.
[70]陈光,臧文臣,刘显清,等.黄芪多糖对动物肿瘤细胞凋亡影响的研究[J].中医药学报,2002,30(4)：55-56.
[71]姚金风,吴春丽,陈慧霞,等.黄芪多糖对HL-60细胞端粒酶活性的作用[J].河南肿瘤学杂志,2005,18(4)：247-248.
[72]刘桂莲,张承玉,刘晓霓,等.黄芪多糖对人胃癌SGC-7901细胞增殖抑制作用的体外研究[J].中国实用医药杂志,2007,2(13)：8-9.
[73]山广志,叶兴涛.注射用黄芪多糖联合化疗治疗84例晚期恶性肿瘤临床疗效观察[J].中国肿瘤临床,2007,34(6)：355-356.
[74]王梅,李秀丽,刘蕊.黄芪多糖在恶性肿瘤治疗中的应用[J].中国中医药科技,2009,16(5)：411-512.
[75]Boyed, MR.1997. The NCI in vitro anticancer drug discovery screen. In Teicher, B.(Ed.).Anticancer drug development guide; preclinical screening, clinical trials and approval, Humana Press, Totowa, p.30.
[76]郑芸,昊敬波.肿瘤化疗增敏剂的研究现状及应用进展[J].西南军医,2010,12(3)：506-508.
[77]王春燕,史书红,唐小卿,等。甲基莲心碱对长春新碱抗肿瘤作用的影响[J].医学临床研究,2004,21(8)：858-861.
[78]侯华新, 黎丹戎, 黄桂宽,等。银杏叶多糖在肿瘤放射,化学治疗中的增敏作用研究[J].广西医科大学学报,2005,1：29-31。
[79]李丽,周庚寅,靳英,等。葡萄籽多酚对多药耐药的逆转作用及其机制[J].山东大学学报：医学版,2004,4：387-389.
[80]Chen B, Sun Q, Wang X, et al.2008. Reversal in multidrug resistance by magnetic nanoparticle of Fe3O4 loaded with adriamycin and tetrandrine in K562/A02 leukemic cells. Int J Nanomedicine.2008;3(2):277-86.
[81]Cassileth BR, Rizvi N, Deng G, Yeung KS, Vickers A, Guillen S, Woo D, Coleton M, Kris MG:Safety and pharmacokinetic trial of docetaxel plus an Astragalus-based herbal formula for non-small cell lung cancer patients. Cancer Chemother Pharmacol 2009,65(1):67-71.
[82]Duan P, Wang ZM:Clinical study on effect of Astragalus in efficacy enhancing and toxicity reducing of chemotherapy in patients of malignant tumor. Zhongguo Zhong Xi Yi Jie He Za Zhi 2002,22(7):515-517.
[83]Zou YH, Liu XM:Effect of astragalus injection combined with chemotherapy on quality of life in patients with advanced non-small cell lung cancer. Zhongguo Zhong Xi Yi Jie He Za Zhi 2003,23(10):733-735.
[84]Zhang ZX, Qi F, Zhou DJ, Liang XY, Zhu LW, Wang PZ:Effect of 5-fluorouracil in combination with Astragalus membranaceus on amino acid metabolism in mice model of gastric carcinoma. Zhonghua Wei Chang Wai Ke Za Zhi 2006, 9(5):445-447.
[85]Cho WC, Leung KN:In vitro and in vivo anti-tumor effects of Astragalus membranaceus. Cancer Lett 2007,8; 252(1):43-54.
[86]Yang M, Qian XH, Zhao DH, Fu SZ:Effects of Astragalus polysaccharide on the erythroid lineage and microarray analysis in K562 cells. J Ethnopharmacol.2010, 127(2):242-250.
[87]陈国辉,黄文凤,等。黄芪的化学成分及药理作用研究进展[J].中国新药杂志,2008,17：1482-1485.
[88]张会杰,熊玉卿,等。P-糖蛋白药物外排作用的研究进展[J].中国临床药理学杂志,2004,4：77-80.
[89]Li H, Yan Z, Ning W, Xiao-Juan G, Cai-Hong Z, Jin-Hua J, Fang M, Qing-Duan W:Using rhodamine 123 accumulation in CD8 cells as a surrogate indicator to study the P-glycoprotein modulating effect of cepharanthine hydrochloride in vivo. J Biomed Biotechnol 2011,2011:281651.
[90]Abuznait AH, Patrick SG, Kaddoumi A:Exposure of LS-180 cells to drugs of diverse physicochemical and therapeutic properties up-regulates P-glycoprotein expression and activity. J Pharm Pharm Sci 2011,14(2):236-248.
[91]Kawami M, Yumoto R, Nagai J, Junyaprasert VB, Soonthornchareonnon N, Patanasethanont D, Sripanidkulchai BO, Takano M:Effect of Thai plant extracts on P-glycoprotein function and viability in paclitaxel-resistant HepG2 cells. Drug Metab Pharmacokinet 2010,25(2):155-162.
[92]Naud J, Michaud J, Leblond FA, Lefrancois S, Bonnardeaux A, Pichette V: Effects of chronic renal failure on liver drug transporters. Drug Metab. Dispos 2008,36(1):124-128.
[93]Nie L, Wu G, Zhang W:Correlation of mRNA expression and protein abundance affected by multiple sequence features related to translational efficiency in Desulfovibrio vulgaris:a quantitative analysis. Genetics 2006,174(4):2229-2243.
[94]Gong J, Jaiswal R, Mathys JM, Combes V, Grau GE, Bebawy M:Microparticles and their emerging role in cancer multidrug resistance. Cancer Treat Rev 2012, 38(3):226-234.
[95]刘选滔,刘德齐。中药及中药提取物逆转肿瘤多药耐药的研究现状[J].现代临床医学,2010,36(3)：166-168.
[1]陈光,臧文臣,刘显清,等.黄芪多糖对动物肿瘤细胞凋亡影响的研究[J].中医药学报,2002,30(4)：55-56.
[2]赵莲华,李清,林梵,等.黄芪多糖协同顾铂对Bel-7404人肝癌细胞的杀伤作用[J].实用癌症杂志,2005,20(1)：34-35.
[3]王宏艳.ERK1/2在黄芪多糖促进HepG2细胞凋亡中的作用[J].中国实验方剂学杂志,2012,18(7)：235-238.
[4]孙聪聪,张英姿,张明,等.黄芪多糖对子宫内膜癌KLE细胞抑制作用的研究[J].中国基层医药,2012,19(10)：1506-1508.
[5]叶媚娜,陈红风,周瑞娟,等.黄芪多糖对基底细胞样乳腺癌细胞增殖和Akt磷酸化的影响[J].中西医结合报,2011,9(12)：1339-1346.
[6]吴志燕,贾岩龙,赵繁荣,等.黄芪多糖组分-A3对HL60白血病细胞的抑制增殖和诱导分化作用[J].时珍国医国药,2012,23(9)：2173-2175.
[7]郑学芝,李佳,王志刚,等.黄芪多糖对COLO205人结肠癌细胞株抑制作用研究[J].中国食物与营养,2012,18(8)：68-70.
[8]许云霞,刘晓健,屈飞,等.中药多糖与过继免疫联合治疗卵巢癌[J].中国实验方剂学杂志,2011,17(21)：231-234.
[9]姚金风,吴春丽,陈慧霞,等.黄芪多糖对HL-60细胞端粒酶活性的作用[J].河南肿瘤学杂志,2005,18(4)：247-248.
[10]许杜娟,陈敏珠.黄芪多糖的抑瘤作用及其机制[J].中国医院药学杂,2005,25(10)：923-925.
[11]Liu X, Yang Y, Zhang X, et al.2010. Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta/Smad in HepG2 cell. J Gastroenterol Hepatol.2010 Feb;25(2):420-6.
[12]刘桂莲,张承玉,刘晓霓,等.黄芪多糖对人胃癌SGC-7901细胞增殖抑制作用的体外研究[J].中国实用医药杂志,2007,2(13)：8-9.
[13][13]谷俊朝,余微波,王字,等.黄芪多糖对TA2小鼠乳腺癌MA-891移植瘤生长及HSP70表达的影响[J].中华肿瘤防治杂志,2006,13(20)：1534-1537.
[14]汪硕.黄芪抗肿瘤作用的实验研究[J].中国现代应用药学杂,2008,25(8)：686-688.
[15]Li J, Bao YX, Zhu X, et al.2008. Immunoregulatory activity of polysaccharopeptide and Astragalus polysaccharides on EAC tumor-bearing mice. Zhongguo Zhong Yao Za Zhi.2008 Apr;33 (8):924-7.
[16]黄宏思,黄卫彤,韦鹏涯,等.黄芪多糖联合顺铂治疗H22肝癌的实验研究[J].广西医科大学学报,2009,26(1)：19-21.
[17]夏星,Dao Nguyen.黄芪多糖对丝裂霉素c(MMC)致骨髓抑制小鼠骨髓及脾脏造血祖细胞的生成作用的影响[J].中国药理学通报,2003,19(7)：812-814.
[18]张琰,程建峰,贺建荣.黄芪多糖对环磷酰胺致小鼠骨髓抑制及毒性的保护作用[J].第四军医大学学报,2003,24(5)：447-448.
[19]章志翔,戚峰,周德俊,等.氟尿嘧啶联合黄芪对小鼠胃癌组织氨基酸代谢的影响[J].中华胃肠外科杂志,2006,9(5)：445.
[20]何月涵,马波,吕亚娜,等.通过血液自体荧光光谱分析探讨黄芪多糖的抑癌作用[J].哈尔滨医科大学学报,2012,46(4)：357-359.
[21]徐尚福,杨天华,吴芹,等.黄芪多糖对环磷酰胺引起小鼠骨髓抑制后造血功能的修复作用[J].遵义医学院报,2011,34(5)：473-476.
[22]邹品文,赵春景,李攀,等.黄芪多糖抗S180肉瘤作用及其免疫调节的影响[J].遵义医学院报,2012,35(1)：17-20.
[23]山广志,叶兴涛.注射用黄芪多糖联合化疗治疗84例晚期恶性肿瘤临床疗效观察[J].中国肿瘤临床,2007,34(6)：355-356.
[24]方晓松,周颦.注射用黄芪多糖治疗原发性肝癌的疗效观察[J].重庆医学,2009,38(8)：935-938.
[25]王梅,李秀丽,刘蕊.黄芪多糖在恶性肿瘤治疗中的应用[J].中国中医药科技,2009,16(5)：411-512.
[26]韩子敏,王巧凤,高福音,等.黄芪川芎嗪注射液加化疗治疗恶性肿瘤36例[J].第四军医大学学报,2006,27(13)：1207.
[27]Guo L, Bai SP, Zhao L, et al.2011. Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer:effects on quality of life and survival. Med Oncol.2011Sep 18.
[28]许敬.注射用黄芪多糖联合甲地孕酮对晚期乳腺癌患者生活质量的影响[J].中国中医药科技,2012,19(2)：182-183.
[29]欧幸甘摇.黄芪多糖预防及治疗宫颈癌化疗所致骨髓抑制的疗效观察[J].吉林医学,2012,35(1)：2774-2775.
[30]刘跃华,黄静,王雍,等.注射用黄芪多糖联合化疗治疗中晚期胃癌的疗效[J].实用医学杂志,2012,27(3)：516-518.
[2]Urruticoechea A, Alemany R, Balart J, Villanueva A, Vinals F, Capella G:Recent advances in cancer therapy:an overview. Curr Pharm Des 2010,16(1):3-10.
[3]Kellof GJ:Perspective on cancer chemoprevention research and drug development. Adv Cancer Res 2000,78:199-334.
[4]Choi CH:ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell Int 2005,5:30.
[5]Wong R, Sagar CM, Sagar SM:Integration of Chinese medicine into supportive cancer care:A modern role for an ancient tradition. Cancer Treat Rev 2001, 27(4):235-246.
[6]Ebinger M, Uhr M. ABC drug transporter at the blood-brain barrier:effects on drug metabolism and drug response[J]. Eur Arch Psychiatry Clin Neurosci,2006, 256(5):294-298,
[7]Fromm MF. Importance of P-glycoprotein at blood-tissue barriers[J]. Trends Pharmacol Sci,2004,25(8):423-429.
[8]Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants[J]. Biochim Biophys Acta,1976, 455(1):152-162.
[9]Demeule M, Regina A, Jodoin J, et al. Drug transport to the brain:key roles for the efflux pump P-glycoprotein in the blood-brain barrier[J]. Vascul Pharmacol, 2002,38(6):339-348.
[10]Schinkel AH, Jonker JW. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family:an overview[J]. Adv Drug Deliv Rev,2003,55(1):3-29.
[11]李睿,海帆.多药耐药蛋白P-糖蛋白的研究进展[J].中国实用医药,2009,4(2)：240-242.
[12]Teda Y, Wada M, Migita T, el al. Increased expression of multi-drug resistance-associated proteins in bladder cancer during clinical course and drug resistance to doxorubicin[J]. Int J Cancer,2002,98:630-635.
[13]Qi F, Li A, Inagaki Y, Gao J, Li J, Kokudo N, Li XK, Tang W:Chinese herbal medicines as adjuvant treatment during chemo-or radio-therapy for cancer. Biosci Trends 2010,4(6):297-307.
[14]Ruan WJ, Lai MD, Zhou JG:Anticancer effects of Chinese herbal medicine, science or myth? J Zhejiang Univ Sci B 2006,7(12):1006-1014.
[15]Konkimalla VB, Efferth T:Evidence-based Chinese medicine for cancer therapy. J Ethnopharmacol.2008,116(2):207-210.
[16]Ji DB, Ye J, Jiang YM, Qian BW:Anti-tumor effect of Liqi, a traditional Chinese medicine prescription, in tumor bearing mice. BMC Complement Altern Med 2009,9:20.
[17]胡军,金伟,杨佩满.p-榄香烯逆转人乳腺癌MCF-7/ADM细胞对阿霉素耐药性的研究[J].中华肿瘤杂志,2004,26(2)：268-270.
[18]沈朋,夏蕾,张海江.逆转肿瘤细胞多药耐药性的四物合剂有效组分[J].中国中药杂志,2005,30(7)：520.
[19]吕淑华。 黄芪多糖抗肿瘤作用研究进展[J].江西中医学院学报,2009,21(1)：85-87.
[20]Balch PA:Prescription for Nutritional Healing, A Practical A-to-Z Reference to Drug-Free Remedies Using Vitamins, Minerals, Herbs and Food Supplements. Fifth Edition, Avery Penguin Putnam Inc., New York, NY, USA,2006.
[21]Rittenhouse JR, Lui PD, Lau BH:Chinese medicinal herbs reverse macrophage suppression induced by urological tumors. J Urol 1991,146(2):486-490.
[22]Ma XQ, Shi Q, Duan JA, Dong TT, Tsim KW:Chemical analysis of Radix Astragali(Huangqi) in China:a comparison with its adulterants and seasonal variations. J Agric Food Chem 2002,50(17):4861-4866.
[23]Shao BM, Xu W, Dai H, Tu P, Li Z, Gao XM:A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb. Biochem Biophys Res Commun 2004,320 (4):1103-1111.
[24]Li J, Bao Y, Lam W, Li W, Lu F, Zhu X, Liu J, Wang H:Immunoregulatory and anti-tumor effects of polysaccharopeptide and Astragalus polysaccharides on tumor-bearing mice. Immunopharmacol Immunotoxicol 2008,30(4):771-782.
[25]Liu X, Yang Y, Zhang X, Xu S, He S, Huang W, Roberts MS:Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta/Smad in HepG2 cell. J Gastroenterol Hepatol 2010,25(2):420-426.
[26]Zhao LH, Ma ZX, Zhu J, Yu XH, Weng DP:Characterization of polysaccharide from Astragalus radix as the macrophage stimulator. Cell Immunol 2011, 271(2):329-334.
[27]World Health Organization (WHO). Medicinal Plants in China. Manila:WHO Regional Publications,1989.
[28]Zee-Cheng RK:Shi-quan-da-bu-tang (ten signifcant tonic decoction), SQT. A potent Chinese biological response modifier in cancer immunotherapy, potentiation and detoxification of anticancer drugs. Methods Find Exp Clin Pharmacol 1992,14(9):725-736.
[29]Cui R, He J, Wang B, Zhang F, Chen G, Yin S, Shen H:Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats. Cancer Chemother Pharmacol 2003,51(1):75-80.
[30]Wang J, Ito H, Shimura K:Enhancing effect of antitumor polysaccharide from Astragalus or Radix hedysarum on C3 cleavage production of macrophages in mice. Jpn J Pharmacol 1989,51 (3):432-434.
[31]Guo L, Bai SP, Zhao L, Wang XH:Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer:effects on quality of life and survival. Med Oncol 2011 Sep 18.
[32]Liu XN, Zhang CY, Jin XD, Li YZ, Zheng XZ, Li L:Inhibitory effect of schisandrin B on gastric cancer cells in vitro. World J Gastroenterol 2007, 13(48):6506-6511.
[33]Zhang G, Shi L, Selke M, Wang X:CdTe quantum dots with daunorubicin induce apoptosis of multidrug-resistant human hepatoma HepG2/ADM cells:in vitro and in vivo evaluation. Nanoscale Res Lett 2011,6(1):418.
[34]Collett A, Tanianis-Hughes J, Warhurst G:Rapid induction of P-glycoprotein expression by high permeability compounds in colonic cells in vitro:a possible source of transporter mediated drug interactions? Biochem Pharmacol 2004,68(4): 783-790.
[35]Mi Y, Lou L:ZD6474 reverses multidrug resistance by directly inhibiting the function of P-glycoprotein. Br J Cancer 2007,97(7):934-940.
[36]Liu XN, Zhang CY, Jin XD, Li YZ, Zheng XZ, Li L. Inhibitory effect of schisandrin B on gastric cancer cells in vitro. World J Gastroenterol,2007; 13(48):6506-6511. PMID:18161920
[37]Xiaoguang C, Hongyan L, Xiaohong L, Zhaodi F, Yan L, Lihua T, Rui H. Cancer chemopreventive and therapeutic activities of red ginseng. Journal of Ethnopharmacology,1998; 60(1):71-78. doi:10.1016/S0378-8741(97)00133-5 PMID:9533434
[38]Gao L, Chen L, Fei XH, Qiu HY, Zhou H, Wang JM. STI571 combined with vincristine greatly suppressed the tumor formation of multidrug-resistant K562 cells in a human-nude mice xenograft model. Chinese Medical Journal (English), 2006; 119(11):911-918. PMID:16780770
[39]王硕,苏杭,袁经权,等。实验小鼠在癌症研究中的应用及其进展[J],中国比较医学杂志,2011,21(9)：63-67.
[40]万继英,韩庶勇.肿瘤实验动物模型的建立及应用研究进展[J].医学综述,2009,15(19)：2959-2961.
[41]施新猷,王四旺,顾为望,等。比较医学[M]。第1版。西安：陕西科学技术出版社,2003,478-480.
[42]中华人民共和国卫生部药政局。 新药(西药)临床前研究指导原则汇编[M]。北京：人民卫生出版社出版,1993,137-139.
[43]刘一, 边原,叶云,等。 阿霉素抗肿瘤作用的研究进展[J].卢州医学院学报,2008,31(1)：101-103.
[44]Xu JH, Deng WL, Fan ZZ:Effects of changwelqing on nuclear translocation of Y-box binding protein-1 and expregslon of P-glycoprotein in human colon cancer cell line with drug-resistance induced by vincristine. Zhongguo Zhong Xi Yi Jie He Za Zhi.2010,30(7):743-747.
[45]An HJ, Wang XY, Yu M, Sheng J, Li PT, Zhang B:Influence of preventing formula for UC on P-gp level in colon tissue of ulcerative colitis in rats. Journal of TCM Univ. of Hunan 2009,29(4):15-17.
[46]Huang CH, Xie ZX, Qin Q:The mechanism of Chinese medicine compound jiexinkang to reverse the multidrug resistance of K562/A02 cells. Journal of TCM Univ. of Hunan 2004,24(1):7-10.
[47]Zhou RF, Liu PX, Tan M:Effect of Astragalus mongholicus injection on proliferation and apoptosis of hormone sensitive (MCF-7) breast cancer cell lines with physiological dose E2. Zhong Yao Cai.2009,32(5):744-747.
[48]Li Q, Bao JM, Li XL, Zhang T, Shen XH:Inhibiting effect of Astragalus polysaccharides on the functions of CD4+CD25 highTreg cells in the tumor microenvironment of human hepatocellular carcinoma. Chin Med J (Engl).2012, 125(5):786-793.
[49]孙曼霁,周廷冲。中国药物研究与发展[M]。第1版。北京：科学出版社, 1996,63-83。
[50]穆玉兰,汤春生,刘鸣,等。实验性持续腹腔化疗裸小鼠人卵巢癌腹腔移植瘤[J]。山东医科大学学报,2000,38(1)：278-280。
[51]赵莲华,李清,林梵,等.黄芪多糖协同顾铂对Bel-7404人肝癌细胞的杀伤作用[J].实用癌症杂志,2005,20(1)：34-35.
[52]谷俊朝,余微波,王字,等.黄芪多糖对TA2小鼠乳腺癌MA-891移植瘤生长及HSP70表达的影响[J].中华肿瘤防治杂志,2006,13(20)：1534-1537.
[53]黄宏思,黄卫彤,韦鹏涯,等.黄芪多糖联合顺铂治疗H22肝癌的实验研究[J].广西医科大学学报,2009,26(1)：19-21.
[54]章志翔,戚峰,周德俊,等.氟尿嘧啶联合黄芪对小鼠胃癌组织氨基酸代谢的影响[J].中华胃肠外科杂志,2006,9(5)：445.
[55]韩子敏,王巧风,高福音,等.黄芪川芎嗪注射液加化疗治疗恶性肿瘤36例[J].第四军医大学学报,2006,27(13)：1207.
[56]黄金明。黄芪对S180荷瘤小鼠的免疫增强及抑瘤作用[J].中国临床免疫学杂志,1995,7(1)：41
[57]张威. 黄芪多糖的免疫促进作用.科学通报,1979,16：764.
[58]赵克胜,丁丽轩,孔海微,等. 黄芪多糖增强人外周血单核细胞产生肿瘤坏死因子的研究[J].中国中西医结合杂志,1993,13(5)：263.
[59]杨巧,庄英帜。肿瘤多药耐药治疗策略：P-qp抑制剂研究进展[J]。海南医学,2011,6：112-115.
[60]Haus-Cohen M, Assaraf YG, Binyamin L, et al. Disruption of P-glycoprotein anticancer drug efflux activity by a small recombinant single-chain Fv antibody fragment targeted to an extracellular epitope[J]. Int J Cancer.2004, 109(5):750-758.
[61]刘嘉,曾庆琪。中药活性成分逆转肿瘤多药耐药的研究进展[J],中医药信息,2011,28(5),112-114.
[62]杨慧莹,赵丽,郭青龙。P-糖蛋白抑制剂的研究进展[J]。实用老年医学,2011,25(2)： 165-169.
[63]柳林,李红,刘欣。中药逆转恶性肿瘤多药耐药的研究进展[J]。山东医药,2008,48(39)：116-117.
[64]Dizdarevic S, Peters AM. Imaging of multidrug resistance in cancer. Cancer Imaging 2011; 11:1-8 [PMID:21362586 DOI:10.1102/1470-7330.2011.0001]
[65]Goda K, Bacso Z, Szabo G. Multidrug resistance through the spectacle of P-glycoprotein. Curr Cancer Drug Targets 2009; 9:281-297 [PMID:19442049 DOI:10.2174/156800909788166493]
[66]Mayur YC, Peters GJ, Prasad VV, Lemo C, Sathish NK. Design of new drug molecules to be used in reversing multidrug resistance in cancer cells. Curr Cancer Drug Targets 2009; 9:298-306 [PMID:19442050 DOI: 10.2174/156800909788166619]
[67]闻镍,张双庆,朱凌,等。P-糖蛋白最新研究进展。中国药事[J],2011,25(7)：718-723.
[68]刘艳.P-糖蛋白与肿瘤多药耐药[J].海南医学,2010,21(1)：117-119.
[69]李峥,庄笑梅,李素云,等.P-糖蛋白中药抑制剂的研究进展[J].2009,25(4)：326-329.
[70]陈光,臧文臣,刘显清,等.黄芪多糖对动物肿瘤细胞凋亡影响的研究[J].中医药学报,2002,30(4)：55-56.
[71]姚金风,吴春丽,陈慧霞,等.黄芪多糖对HL-60细胞端粒酶活性的作用[J].河南肿瘤学杂志,2005,18(4)：247-248.
[72]刘桂莲,张承玉,刘晓霓,等.黄芪多糖对人胃癌SGC-7901细胞增殖抑制作用的体外研究[J].中国实用医药杂志,2007,2(13)：8-9.
[73]山广志,叶兴涛.注射用黄芪多糖联合化疗治疗84例晚期恶性肿瘤临床疗效观察[J].中国肿瘤临床,2007,34(6)：355-356.
[74]王梅,李秀丽,刘蕊.黄芪多糖在恶性肿瘤治疗中的应用[J].中国中医药科技,2009,16(5)：411-512.
[75]Boyed, MR.1997. The NCI in vitro anticancer drug discovery screen. In Teicher, B.(Ed.).Anticancer drug development guide; preclinical screening, clinical trials and approval, Humana Press, Totowa, p.30.
[76]郑芸,昊敬波.肿瘤化疗增敏剂的研究现状及应用进展[J].西南军医,2010,12(3)：506-508.
[77]王春燕,史书红,唐小卿,等。甲基莲心碱对长春新碱抗肿瘤作用的影响[J].医学临床研究,2004,21(8)：858-861.
[78]侯华新, 黎丹戎, 黄桂宽,等。银杏叶多糖在肿瘤放射,化学治疗中的增敏作用研究[J].广西医科大学学报,2005,1：29-31。
[79]李丽,周庚寅,靳英,等。葡萄籽多酚对多药耐药的逆转作用及其机制[J].山东大学学报：医学版,2004,4：387-389.
[80]Chen B, Sun Q, Wang X, et al.2008. Reversal in multidrug resistance by magnetic nanoparticle of Fe3O4 loaded with adriamycin and tetrandrine in K562/A02 leukemic cells. Int J Nanomedicine.2008;3(2):277-86.
[81]Cassileth BR, Rizvi N, Deng G, Yeung KS, Vickers A, Guillen S, Woo D, Coleton M, Kris MG:Safety and pharmacokinetic trial of docetaxel plus an Astragalus-based herbal formula for non-small cell lung cancer patients. Cancer Chemother Pharmacol 2009,65(1):67-71.
[82]Duan P, Wang ZM:Clinical study on effect of Astragalus in efficacy enhancing and toxicity reducing of chemotherapy in patients of malignant tumor. Zhongguo Zhong Xi Yi Jie He Za Zhi 2002,22(7):515-517.
[83]Zou YH, Liu XM:Effect of astragalus injection combined with chemotherapy on quality of life in patients with advanced non-small cell lung cancer. Zhongguo Zhong Xi Yi Jie He Za Zhi 2003,23(10):733-735.
[84]Zhang ZX, Qi F, Zhou DJ, Liang XY, Zhu LW, Wang PZ:Effect of 5-fluorouracil in combination with Astragalus membranaceus on amino acid metabolism in mice model of gastric carcinoma. Zhonghua Wei Chang Wai Ke Za Zhi 2006, 9(5):445-447.
[85]Cho WC, Leung KN:In vitro and in vivo anti-tumor effects of Astragalus membranaceus. Cancer Lett 2007,8; 252(1):43-54.
[86]Yang M, Qian XH, Zhao DH, Fu SZ:Effects of Astragalus polysaccharide on the erythroid lineage and microarray analysis in K562 cells. J Ethnopharmacol.2010, 127(2):242-250.
[87]陈国辉,黄文凤,等。黄芪的化学成分及药理作用研究进展[J].中国新药杂志,2008,17：1482-1485.
[88]张会杰,熊玉卿,等。P-糖蛋白药物外排作用的研究进展[J].中国临床药理学杂志,2004,4：77-80.
[89]Li H, Yan Z, Ning W, Xiao-Juan G, Cai-Hong Z, Jin-Hua J, Fang M, Qing-Duan W:Using rhodamine 123 accumulation in CD8 cells as a surrogate indicator to study the P-glycoprotein modulating effect of cepharanthine hydrochloride in vivo. J Biomed Biotechnol 2011,2011:281651.
[90]Abuznait AH, Patrick SG, Kaddoumi A:Exposure of LS-180 cells to drugs of diverse physicochemical and therapeutic properties up-regulates P-glycoprotein expression and activity. J Pharm Pharm Sci 2011,14(2):236-248.
[91]Kawami M, Yumoto R, Nagai J, Junyaprasert VB, Soonthornchareonnon N, Patanasethanont D, Sripanidkulchai BO, Takano M:Effect of Thai plant extracts on P-glycoprotein function and viability in paclitaxel-resistant HepG2 cells. Drug Metab Pharmacokinet 2010,25(2):155-162.
[92]Naud J, Michaud J, Leblond FA, Lefrancois S, Bonnardeaux A, Pichette V: Effects of chronic renal failure on liver drug transporters. Drug Metab. Dispos 2008,36(1):124-128.
[93]Nie L, Wu G, Zhang W:Correlation of mRNA expression and protein abundance affected by multiple sequence features related to translational efficiency in Desulfovibrio vulgaris:a quantitative analysis. Genetics 2006,174(4):2229-2243.
[94]Gong J, Jaiswal R, Mathys JM, Combes V, Grau GE, Bebawy M:Microparticles and their emerging role in cancer multidrug resistance. Cancer Treat Rev 2012, 38(3):226-234.
[95]刘选滔,刘德齐。中药及中药提取物逆转肿瘤多药耐药的研究现状[J].现代临床医学,2010,36(3)：166-168.
[1]陈光,臧文臣,刘显清,等.黄芪多糖对动物肿瘤细胞凋亡影响的研究[J].中医药学报,2002,30(4)：55-56.
[2]赵莲华,李清,林梵,等.黄芪多糖协同顾铂对Bel-7404人肝癌细胞的杀伤作用[J].实用癌症杂志,2005,20(1)：34-35.
[3]王宏艳.ERK1/2在黄芪多糖促进HepG2细胞凋亡中的作用[J].中国实验方剂学杂志,2012,18(7)：235-238.
[4]孙聪聪,张英姿,张明,等.黄芪多糖对子宫内膜癌KLE细胞抑制作用的研究[J].中国基层医药,2012,19(10)：1506-1508.
[5]叶媚娜,陈红风,周瑞娟,等.黄芪多糖对基底细胞样乳腺癌细胞增殖和Akt磷酸化的影响[J].中西医结合报,2011,9(12)：1339-1346.
[6]吴志燕,贾岩龙,赵繁荣,等.黄芪多糖组分-A3对HL60白血病细胞的抑制增殖和诱导分化作用[J].时珍国医国药,2012,23(9)：2173-2175.
[7]郑学芝,李佳,王志刚,等.黄芪多糖对COLO205人结肠癌细胞株抑制作用研究[J].中国食物与营养,2012,18(8)：68-70.
[8]许云霞,刘晓健,屈飞,等.中药多糖与过继免疫联合治疗卵巢癌[J].中国实验方剂学杂志,2011,17(21)：231-234.
[9]姚金风,吴春丽,陈慧霞,等.黄芪多糖对HL-60细胞端粒酶活性的作用[J].河南肿瘤学杂志,2005,18(4)：247-248.
[10]许杜娟,陈敏珠.黄芪多糖的抑瘤作用及其机制[J].中国医院药学杂,2005,25(10)：923-925.
[11]Liu X, Yang Y, Zhang X, et al.2010. Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta/Smad in HepG2 cell. J Gastroenterol Hepatol.2010 Feb;25(2):420-6.
[12]刘桂莲,张承玉,刘晓霓,等.黄芪多糖对人胃癌SGC-7901细胞增殖抑制作用的体外研究[J].中国实用医药杂志,2007,2(13)：8-9.
[13][13]谷俊朝,余微波,王字,等.黄芪多糖对TA2小鼠乳腺癌MA-891移植瘤生长及HSP70表达的影响[J].中华肿瘤防治杂志,2006,13(20)：1534-1537.
[14]汪硕.黄芪抗肿瘤作用的实验研究[J].中国现代应用药学杂,2008,25(8)：686-688.
[15]Li J, Bao YX, Zhu X, et al.2008. Immunoregulatory activity of polysaccharopeptide and Astragalus polysaccharides on EAC tumor-bearing mice. Zhongguo Zhong Yao Za Zhi.2008 Apr;33 (8):924-7.
[16]黄宏思,黄卫彤,韦鹏涯,等.黄芪多糖联合顺铂治疗H22肝癌的实验研究[J].广西医科大学学报,2009,26(1)：19-21.
[17]夏星,Dao Nguyen.黄芪多糖对丝裂霉素c(MMC)致骨髓抑制小鼠骨髓及脾脏造血祖细胞的生成作用的影响[J].中国药理学通报,2003,19(7)：812-814.
[18]张琰,程建峰,贺建荣.黄芪多糖对环磷酰胺致小鼠骨髓抑制及毒性的保护作用[J].第四军医大学学报,2003,24(5)：447-448.
[19]章志翔,戚峰,周德俊,等.氟尿嘧啶联合黄芪对小鼠胃癌组织氨基酸代谢的影响[J].中华胃肠外科杂志,2006,9(5)：445.
[20]何月涵,马波,吕亚娜,等.通过血液自体荧光光谱分析探讨黄芪多糖的抑癌作用[J].哈尔滨医科大学学报,2012,46(4)：357-359.
[21]徐尚福,杨天华,吴芹,等.黄芪多糖对环磷酰胺引起小鼠骨髓抑制后造血功能的修复作用[J].遵义医学院报,2011,34(5)：473-476.
[22]邹品文,赵春景,李攀,等.黄芪多糖抗S180肉瘤作用及其免疫调节的影响[J].遵义医学院报,2012,35(1)：17-20.
[23]山广志,叶兴涛.注射用黄芪多糖联合化疗治疗84例晚期恶性肿瘤临床疗效观察[J].中国肿瘤临床,2007,34(6)：355-356.
[24]方晓松,周颦.注射用黄芪多糖治疗原发性肝癌的疗效观察[J].重庆医学,2009,38(8)：935-938.
[25]王梅,李秀丽,刘蕊.黄芪多糖在恶性肿瘤治疗中的应用[J].中国中医药科技,2009,16(5)：411-512.
[26]韩子敏,王巧凤,高福音,等.黄芪川芎嗪注射液加化疗治疗恶性肿瘤36例[J].第四军医大学学报,2006,27(13)：1207.
[27]Guo L, Bai SP, Zhao L, et al.2011. Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer:effects on quality of life and survival. Med Oncol.2011Sep 18.
[28]许敬.注射用黄芪多糖联合甲地孕酮对晚期乳腺癌患者生活质量的影响[J].中国中医药科技,2012,19(2)：182-183.
[29]欧幸甘摇.黄芪多糖预防及治疗宫颈癌化疗所致骨髓抑制的疗效观察[J].吉林医学,2012,35(1)：2774-2775.
[30]刘跃华,黄静,王雍,等.注射用黄芪多糖联合化疗治疗中晚期胃癌的疗效[J].实用医学杂志,2012,27(3)：516-518.