橙皮甙对人肺腺癌A549/DDP细胞增殖的影响
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摘要
目的：以人肺腺癌A549/DDP细胞株为受试对象,研究橙皮甙对人肺腺癌A549/DDP细胞增殖的抑制作用及其细胞凋亡(apoptosis,APO)的影响,旨在进一步阐明橙皮甙的抗肿瘤机制,为其应用于肺癌的临床治疗提供更多的实验依据。方法：①通过细胞计数法来绘制A549和A549/DDP细胞的生长曲线;3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐法(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide,MTT)来测定A549/DDP对顺铂(cis-platin,DDP)的耐药倍数；采用MTT法测定橙皮甙对A549和A549/DDP细胞的增殖抑制作用,计算出橙皮甙对两细胞系的半数抑制浓度,比较有无差异。②用接近半数抑制浓度的橙皮甙处理A549/DDP细胞24h后,经PI(propidium iodide, PI)荧光染料染色后,用流式细胞术(flow cytometric methods,FCM)分析细胞周期。③用0、6、12、24、48和96mg/L橙皮甙处理A549/DDP细胞24h后,在荧光显微镜下观察细胞形态学的变化及FCM检测细胞凋亡的情况。结果：①亲代A549细胞和A549/DDP细胞的生长曲线相似,倍增时间分别为(33.68±0.11)h和(33.54±0.84)h,两组细胞数比较无统计学差异性(P>0.05)；经DDP处理A549和A549/DDP细胞48h后,橙皮甙对A549/DDP细胞的抑制率明显高于对A549细胞的抑制率,两组比较有统计学差异性(P<0.05)。橙皮甙对A549和A549/DDP细胞的半数抑制浓度(50% concentration of inhibition,IC50)分别为12.68μmol/L和163.54μmol/L, A549/DDP细胞对DDP的耐药倍数为12.90。②用不同浓度的橙皮甙对A549/DDP细胞进行干预,在不同时间测得其对A549/DDP细胞的抑制率呈现了随着橙皮甙浓度的增加和(或)时间的延长橙皮甙对A549/DDP的抑制率增强,呈剂量时间依赖性。③用24mg/L的橙皮甙作用A549/DDP细胞24h后,实验组G2/M期和S期细胞数与对照组细胞数比较有统计学差异性(P<0.05),G0/G1期两组细胞数比较无统计学差异性(P>0.05)。④用不同浓度的橙皮甙处理A549/DDP细胞24h,染色后显示A549/DDP细胞核缩小变形,致密浓染,荧光成团块分布；经FCM检查凋亡细胞数所占的百分比,显示出明显的剂量依赖关系(P<0.05)。结论：①A549/DDP细胞基本保留了亲代细胞的生长特性,但相对于其亲代细胞系A549,确实对传统化疗药物DDP产生明显的耐药性。②橙皮甙对A549/DDP有生长抑制作用,并呈剂量、时间依赖性,A549/DDP对橙皮甙不具有耐药性。③橙皮甙可诱导A549/DDP细胞周期阻滞于G2/M期。④橙皮甙能诱导A549/DDP细胞凋亡。
Objective:To explore anti-proliferative of and proapoptic effects of hesperidin on lung adenocarcinomas cell line A549/DDP. Methods:①Growth curves of A549 and A549/DDP cell lines were plotted, and MTT assay was applied to evaluate the resistance index of A549/DDP cell line to cisplatin. With the same assay, IC50 values of hesperidin of both cell lines were calculated.②A549/DDP cell cycle analysis was detected by flow cytometry 24h after hesperidin treatment at the concentration close to IC50.③After 24h treatment of hesperidin at various concentrations, A549/DDP morphologic changes were observed under fluorescence microscope and the apoptotic ratos were measured by flow cytometry. Results:①The cell growth curve of A549 was similar to that of A549/DDP. The doubling generation time of A549 and A549/DDP were (33.68±0.11)h and (33.54±0.84)h, respectively(P> 0.05). After 48h treatment with cisplatine, IC50 values of cisplatine to A549 cell line and A549/DDP cell line were 12.68μmol/L and 163.54μmol/L respectively. Consequently, the resistance index of A549/DDP to cisplatine was defined as 12.90.(2)A549 and A549/DDP proliferations were dose-and time-dependently inhibted(P< 0.05) following 48h treatment with hesperidin.③After 24h treatment with 24mg/L of hesperidin, there is a pronounced decrease of the cell rate in S phase, along with a significant arrest in G2/M phase.④Under fluorescence microscope, A549/DDP cell line treated with hesperidin showed shrunk or distorted nucleus with fluorescence conglomerated like grains in them. And the apoptotic rate of A549/DDP increased as the concentration of hesperidin increased. Conclusions:①A549/DDP cell line has similar growth property with its parental cell line A549. A549/DDP is more resistant to traditional chemotherapeutics cisplatin.②Hesperid-in may inhibit A549 and A549/DDP from proliferation dose-and time-dependently. A549/DDP is sensitive to hesperidin.③Hesperidin may cause A549/DDP arrest in G2/M phase.④Hesperidin may induce A549/DDP cell line apoptosis.
Objective:To explore anti-proliferative of and proapoptic effects of hesperidin on lung adenocarcinomas cell line A549/DDP. Methods:①Growth curves of A549 and A549/DDP cell lines were plotted, and MTT assay was applied to evaluate the resistance index of A549/DDP cell line to cisplatin. With the same assay, IC50 values of hesperidin of both cell lines were calculated.②A549/DDP cell cycle analysis was detected by flow cytometry 24h after hesperidin treatment at the concentration close to IC50.③After 24h treatment of hesperidin at various concentrations, A549/DDP morphologic changes were observed under fluorescence microscope and the apoptotic ratos were measured by flow cytometry. Results:①The cell growth curve of A549 was similar to that of A549/DDP. The doubling generation time of A549 and A549/DDP were (33.68±0.11)h and (33.54±0.84)h, respectively(P> 0.05). After 48h treatment with cisplatine, IC50 values of cisplatine to A549 cell line and A549/DDP cell line were 12.68μmol/L and 163.54μmol/L respectively. Consequently, the resistance index of A549/DDP to cisplatine was defined as 12.90.(2)A549 and A549/DDP proliferations were dose-and time-dependently inhibted(P< 0.05) following 48h treatment with hesperidin.③After 24h treatment with 24mg/L of hesperidin, there is a pronounced decrease of the cell rate in S phase, along with a significant arrest in G2/M phase.④Under fluorescence microscope, A549/DDP cell line treated with hesperidin showed shrunk or distorted nucleus with fluorescence conglomerated like grains in them. And the apoptotic rate of A549/DDP increased as the concentration of hesperidin increased. Conclusions:①A549/DDP cell line has similar growth property with its parental cell line A549. A549/DDP is more resistant to traditional chemotherapeutics cisplatin.②Hesperid-in may inhibit A549 and A549/DDP from proliferation dose-and time-dependently. A549/DDP is sensitive to hesperidin.③Hesperidin may cause A549/DDP arrest in G2/M phase.④Hesperidin may induce A549/DDP cell line apoptosis.
引文
[1]吴在德,吴肇汉.外科学[M].北京：人民卫生出版社,2006:356-357.
[2]Parkin DM.Global cancer statistics in the year 2000[J].Cancet Oncol,2001,2(9):533-543.
[3]董志伟,乔友林,李连弟,等.中国癌症控制策略研究报告[J].中国肿瘤,2002,11(5):250-260.
[4]Mountain C F.Revisions in the international system for staging lung cancer[J].Chest, 1997,111:1710-1717.
[5]Kawai H,Kiura k,Tabata M,et al.Characterization of non-small-cell lung cancer cell lines established before and after chemotherapy[J].Lung Cancer,2002,35(3):305-314.
[6]Edelman M J,Gandara D R,Roachm R D,et al.Multimodality therapy in stage III non-small cell lung cancer[J].Ann Thorac Surg,1996,61 (5):1564-1572.
[7]Rosell,Gomez C J,Camps C,et al.Pieresectional chemotherapy in stage IIIA non-small-cell lung cancer:a 7 year assessment of a randomized controlled trial[J].Lung Cancer, 1999,26(1):7-14.
[8]Spasova I,Petera J,Hytych V.The role of neoadjuvant chemotherapy in marginally resectable or unresectable stage III non-small-cell lung cancer[J].Neoplasma,2002,49 (3):189-196.
[9]Non-small Cell Lung Cancer Collaborative Group.Chemotherapy in non-small cell lung cancer:a meta-analysis using updated individual patient data from 52 randomised clinical trials[J].Br Med. J,1995,311(7):899-909.
[10]中国医师协会胸外科医师分会.基于循证医学的肺癌诊断新进展[C].中国医师协会胸外科医师分会2008年年会论文集,2008:63-70.
[11]Kerr J F,W interford C M,Harmon B V.Apoptosis,its signi-ficance in cancer and cancer therapy [J].Cancer,1994,73(8):2013-2026.
[12]余晓,钱民章.HPLC法测定遵义产两种柑橘果皮中橙皮甙含量[J].遵义医学院学报,2005,28(2)：175-177.
[13]江纪武,肖庆祥.植物药有效成分手册[M].北京：人民卫生出版社,1986.561-562.
[14]Guardia T,Rotelli A E,Juarez A O,et al.Anti-inflammatory properties of plant flavonoids. Effects of rutin,quercetin and hesperidin on adjuvant arthritis in rat [J].IL Farmaco,2001,56(3):683-687.
[15]于辉,李春香,甘庆贤.陈皮的药理作用[J].生物磁学,2005,5(1):44-45.
[16]蓝航莲,孙树侠.柑橘类黄酮的生理活性和研究进展[J].中国食物与营养,2003(7):15-18.
[17]Tanaka T,Makita H,Ohnishi M,et al.Chemoprevention of 4-nitroquino line 1- oxide-induced oral carcinogenesis in rats by flavonoids diosmin and hesperidin,each alone and in combination[J].Cancer Res.1997,57(15):246-252.
[18]Tanaka T,Kohno H,Murakami M,et al.Suppression of azoxymethane-induced colon arcinogenesis in male F344 rats by mandarin juices rich in(3-crypt-oxanthin and hesperidin[J].Int. J.Cancer,2000,88:146-150.
[19]Keiko S,Yoshinobu H,Zheng Q,et al.Inhibition of inducible isoforms of cyclo-oxygen-ase and nitricoxide synthase by flavonoid hesperidin in mouse macrophage cell line[J]. Cancer Letters,2003,199(2):139-145.
[20]Park H J,Kim M J,Ha E,et al.Apoptotic effect of hesperidin through caspase 3 activ-ation in human colon cancer cells,SNU-C4[J].Phytomedicine,2008,15(1-2):147-51.
[21]Kim M J, Park H J,Hong M S,et al.Citrus reticulata Blanco induces apoptosis in human gastric cancer cells SNU-668[J].Nutr. Cancer,2005,51(18):78-82.
[22]张天泽,徐光炜.肿瘤学(上册).第二版[M].天津：天津科学技术出版社；沈阳：辽宁科学技术出版社,2005,842.
[23]鄂征.组织培养和分子细胞学技术[M].北京：科学出版社,1994.164-169.
[24]李曦,郭先健,黄桂君,等.人肺腺癌多药抗药细胞系LC23/CDDP细胞周期及DNA含量变化[J].河南肿瘤学杂志,1997,10(2):93-95.
[25]陈鹏,刘叙仪,赫复生.耐顺铂人肺腺癌细胞系A549/CDDP的建立及耐药机制[J].中国肿瘤临床,1995,3(4):582-587.
[26]张天泽,徐光炜.肿瘤学(上册).第二版[M].天津：天津科学技术出版社；沈阳：辽宁科学技术出版社,2005,210.
[27]顾后,贾勇.中药对肺癌细胞增殖与凋亡影响的研究进展[J].云南中医中药杂志,2007,28(5):42-44.
[28]孙玺媛,孙建立.益气养阴方逆转人肺腺癌A549/DDP多药耐药机理[J].实用肿瘤学杂志,2009,23(1)99:26-29.
[29]张天泽,徐光炜.肿瘤学(上册).第二版[M].天津：天津科学技术出版社；沈阳：辽宁科学技术出版社,2005,253.
[1]吴一龙,张明和,廖美琳,等.肺癌的诊断和分期临床指导[J].中国肺癌杂志,2003,6(5):330-334.
[2]杨宏健.天然药物化学[M].郑州：河南科学技术出版社,2007,83-89.
[3]叶任高,陆再英.内科学[M].北京：人民卫生出版社,2004:116-117.
[4]Kaufmann J A,Bickford P C,Taglialatela G.Free radical-dependent change in con-stitutive nuclear factor kappa B in the aged hippocampus[J].Neuroreport,2002,13(15): 1971-1978.
[5]陈国有,齐鹤,徐东花.黄酮类化合物的生物活性研究进展[J],黑龙江医药,2008,21(3):61-63.
[6]Stanisalw Burda,Wieslaw Oleszek.Antioxidant and antiradical activities of flavonoids [J],J A gric Food Chem,2001,49(6):274-279.
[7]Ha Sook Chung.Flavonoid constituents of chorizan the diffusa with potential cancer chemopreventive activity[J].J A gric Food Chem,1999,47(1):36-41.
[8]刘宏,赵金垣.自由基在理化因素致肺癌中的作用[J].环境与健康杂志,2008,25(1)：85-87.
[9]Mercedes.Oxidation of the flavonol quercetin by polyphenol oxidase[J].J Agric Food Chem.1999,47(1):56-60.
[10]张德权,台建祥,付勤,等.生物类黄酮的研究及应用概况[J].食品与发酵工业,1999,25(6)：52-56.
[11]Beate Baderschneider.Isolation and characterization of novel benzoates,cinnamates, flavonoids and lingmans from riesling wine and screening for antioxidant activity[J].J Agric Food Chem.2001,49(6):2788-2798.
[12]Rahman I,Biswas SK,Kirkham PA.Regulation inflammation and redox signaling by dietary polyphenols[J].Biochem Pharmacol,2006,72(11):1439-1452.
[13]王斌.食品中的免疫调节功能因子研究进展[J].氨基酸和生物资源,2009,31(1):70-73.
[14]Nanua S,Zick SM,Andrade JE,et al.Quercetin blocks airway epithelial cell chemokine expression[J].Am J Respir Cell Mol Biol,2006,35(5):602-610.
[15]唐嘉航,叶希韵,刘江,等.银杏叶总黄酮对胰岛素抵抗大鼠糖脂代谢和肝功能的影响[J].上海交通大学学报(医学版),2009,29(2)：150-154.
[16]Di Paola R,Mazzon E,Muia C,et al.Protective effect of HyPerieum perforatum in zymosan-induced multiple organ dysfunction syndrome:relationship to its in hibitory effect on nitric oxide production and its peroxynitrite scavenging activity[J].Nitrc Oxide,2007,16(1):118-130.
[17]Kumar P,Khanna M,Srivastava V,et al.Effect of quercetin supplementation on lung antioxidants after experimental influenza virus infection[J].Exp Lung Res,2005,31(5): 449-459.
[18]Giakoustidis AE,Giakoustidis DE,Iliadis S,et al.Attenuation of intestinal ischeia/re-perfudion induced liver and lung injury by intraperitoneal administration of (-)-epigallocatechin-3-gallate[J].Free Radic Res,2006,40(1):103-110.
[19]汪德清,房征宇,沈文梅,等.黄芪总黄酮抗紫外线损伤作用的实验研究[J].劳动医学,1998,5(4)：200-202.
[20]汪德清,沈文梅,田亚平,等.黄芪总黄酮对γ射线所致V79细胞DNA链断裂损伤防护作用的实验研究[J].中华放射医学与防护杂杂志,1995,1(2):106-107.
[21]齐琳,刘春宇,吴文倩,等.沙苑子黄酮对60Coγ射线损伤作用的影响[J].苏州大学学报(医学版),2008,28(1):26-29.
[22]金宏,刘丽,王先远,等.大豆异黄酮抗辐射作用的实验研究[J].氨基酸和生物资源,2004,26(3):23-26.
[23]孙维琦,郭英,袁小洁,等.大豆复合物对丫射线辐射损伤防护作用[J].中国公共卫生,2007,23(10)：1165-1166.
[24]张氽,阚建全.陈宗道生物类黄酮抗癌作用研究进展[J].中国野生植物资源,2003,22(4)：8-11.
[25]龙奇达,熊绍权,赵霞.槲皮素的癌化学预防和抗肿瘤作用研究进展[J].中华妇幼临床医学杂志,2008,4(4):56-59.
[26]高昕,王喜军.黄酮类化合物抗肿瘤作用研究进展[J].中医药信息,2005,22(5):33-34.
[27]黄华艺,查锡良.黄酮类化合物抗肿瘤作用研究进展[J].中国新药与临床杂,2002,21(7)：428-433.
[28]Balakrishnan A,Menon VP.Protective effect of hesperidin on nicotine induced toxicity in rats[J].Indian J Exp Biol,2007,45(2):194-202.
[29]Syed DN,Afaq F,Kweon MH,et al.Green to apolyphenol EGCG suppresses cigarette smoke condendate-induced NF-kappaB activation in normal human bronchial epith-elial cells[J].Oncogene,2007,26(5):673-682.
[30]邬海桥,周向.植物黄酮类的生物学特性及对呼吸系统疾病的影响[J].国际中医中药杂志,2007,29(4):223-226.
[31]Pang GG,Li ZH,Bai J,et al.Literature review of researches on physiological effects of Hesperidin[J].Nonwood Forest Res,2006,24 (4):83-86.
[32]卢波安,喜峰.中药抗肿瘤作用的研究[J].中国初级卫生保健,2008,22(9):72-73.
[33]秦善文,郑玉玲.抗肿瘤中药实验研究进展[J].河南中医,2005,25(2):76-78.
[34]赵金香,杨连玉,袁钠.大豆黄酮在畜牧生产中的研究及应用[J].吉林畜牧兽医,2003,4：4-6.
[35]胡成穆,陈琳,李荣,等.豹皮樟总黄酮对免疫低下小鼠免疫功能的影响[J].中国药理学通报,2007,23(6)：804-808.
[36]张莉,陈乃富,谷仿丽,等.蕨菜黄酮提取物免疫调节作用的实验研究[J].中国中医药科技,2009,16(1)：30-31.
[37]Saha P,Banerjee S,Ganguly C,et al.Black tea estract can modulate protein expression of H-ras,c-myc,p53,and Bcl-2 genes during pulmonary hyperplasia,dysplasia,dys-plasia, and carcinoma in situ[J].J Enciron Pathol Toxicol Oncol,2005,24(3):211-244.
[38]Yeh SL,Wu SH.Effects of quercetin on beta-apo-8-carotenal-induced DNA damage and cytochrome P1A2 expression in A549 cells[J].Chem Biol Interact,2006,163(3): 199-206.
[39]杨博,李志裕,尤启冬.黄酮类化合物的抗肿瘤作用机制研究进展[J].药学进展,2008,32(9)：391-397.
[40]李丽波,刘耕陶.硫氧还蛋白的生物学及其与阿尔茨海默病和帕金森病的关系[J].药学学报,2008,43(1)：1-8.
[41]Lu J,Papp L V,Fang J G,et al.Inhibition of mammalian thioredoxin reductase by some flavonoids:implications for myricetin and quercetin anticancer activity[J].Cancer Res, 2006,66(8):4410-4418.
[42]闫伟,吴波.DNA拓扑异构酶Ⅱ与细胞增殖[J].医学研究生学报,2004,17(6):535-538.
[43]王晨,张立实,何涛.染料木黄酮对体外细胞增殖的抑制作用研究[J].中国公卫生,2002,18(9)：1056-1058.
[44]杨小凤,雷海民,付宏征,等.栾树种子中黄酮类化学成分[J].药学学报,2000,35(3):208-211.
[45]Quintin J,Roullier C,Thoret C,et al.Synthesis and antitubulin evaluation of chromone-based analogues of combretastatins[J].Tetrahedron,2006,62(17):4038-4051.
[46]宋悦,沈铿.新型小分子细胞周期素抑制剂flavopiridol在肿瘤治疗中的应用[J].中华医学杂志,2005,85(12):862-864.
[47]Kalpana S,Maggie J,Rathos J.PravinMahajan:P276-00,a novel cyclindependent in-hibitor induces G1-G2 arrest,shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models [J].Mol Cancer Ther,2007,6(3):26-34.
[48]Sanchez-Martinez C,Shih C,Zhu G,et al.Studies on cyclindependent kinase inhibitors: indole-[2,3-a]pyrrolo[3,4-c]carbazoles versus bisindolylmalei-mides[J]. Bio org Med Chem Lett,2003,13(21):3841-3846.
[49]Kalpana S,Joshi.In vitro antitumor properties of a novel cyclindependent kinase in-hibitor,P276-00[J].Mol Cancer Ther,2007,6(3):918-982.
[50]朱婷,汪希鹏,马庆良.芳香化酶抑制剂治疗妇科恶性肿瘤进展[J].国际妇产科学杂志,2008,35(5):341-344.
[51]周向东,蔡文琴.芳香化酶mRNA在肺癌组织中表达的初步研究[J].中国肺癌杂志,2000,3(4)：269-271.
[52]周向东,蔡文琴,曹红卫.男性肺癌患者外周血性激素水平及其与肺癌组织中芳香化酶表达的相关性研究[J].癌症,2002,21(3):259-262.
[53]Ta N,Walle T.Aromatase inhibition by bioavailable methylated flavones[J].J Steroid Biochem Mol Biol,2007,107(122):127-129.
[54]苏莉莎,骆文龙.植物雌激素的作用[J].生命的化学,2006,26(1):58-59.
[55]马吉祥,李会庆.植物雌激素与肿瘤[J].国外医学肿瘤学分册,2001,28(6):416-420.
[56]周利红,李琦,唐中祥.中医药调控肿瘤信号转导的研究现状与思考[J].上海中医药大学学报,2008,22(6):77-81.
[57]邢雁霞,刘斌钰.受体型TPK-Ras-MAPK信号转导途径研究进展[J].大同医学专科学校学报,2006,26(1):42-43.
[58]陆涛,卢帅,李慧芳,等.肿瘤信号转导通路及相关药物研发的现状与展望(上)[J].中国药科大学学报,2008,39(3)：193-199.
[59]陆涛,卢帅,李慧芳,等.肿瘤信号转导通路及相关药物研发的现状与展望(下)[J].中国药科大学学报,2008,39(3)：289-300.
[60]LoPiccolo J,Granville CA,Gills JJ,et al.Targeting Akt in cancer therapy[J].Anticancer Drugs,2007,18(8):861-874.
[61]Zhang X,Jin B,Huang C.The PI3K/Akt pathway and its downstream transcriptional factors as targets for chemoprevention[J].Curr Cancer Drug Targets,2007,7(4):305-316.
[62]张百川,孟祥晨,张明江.表没食子儿茶素没食子酸酯对增殖性疾病生长因子的诱捕作用[J].中草药,2009,38(1):151-153.
[63]Kobayashi S,Shimamura T,Monti S,et al.Transcriptional profiling identifies cyelin D1 as a critical downstream effector of mutant epidermal growth factor receptor signal-ing[J].Cancer Res,2006,66(23):11389-11398.
[64]Nakahata N,Kyo R,Kutsuwa M,et al.Inhibition of mitogen-activated protein kinase cascade by baicalein,a flavonoid of natural origin[J].Nippon Yakurigaku Zasshi,1999, 114(Suppll):215-219.
[65]Hemstrom TH,Sandstrom M,Zhivotovsky B.Inhibitors of the PI3-kinase/Akt pathway induce mitotic catastrophe in non-smll cell lung cancer cells[J].Int J Cancer,2006, 119(5):1028-1038.
[66]Lee HY,Oh SH,Woo JK,et al.Chemopreventive effects of deguelin,a novel Akt in-hibitor,on tobacco-induced lung tumorigenesis[J].J Natl Cancer Inst,2005,97(22): 1695-1699.
[67]Lee YK,Isham CR,Kaufman SH,et al.Flavopiridol disrupts STAT3/DNA inter-actions,attenuates STAT3-directed transcription,and combines with the Jak kinase inhibitor AG490 to achieve cytotoxic synergy[J].Mol Cencer Ther,2006,5(1):138-148.
[68]Li Y,Ahmed F,Ali S,et al.Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemptherapeutic agents in human cancer cells[J].Cancer Res,2005,65(15):6934-6942.
[69]Ferrara N.Vascular endothelial growth factor as a target for anticancer therapy[J]. Oncologist,2004,9:2-10.
[70]Zhang Y Y,Shen S R.Inhibitory effects of tea catechins on tumor angiogenesis[J]. Chin J Cell Biol,2005,27(25):267-272.
[71]Nam S,Smith D M,Dou Q P.Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo[J].J Biol Chem,2001,276:13322-13330.
[72]施明.类黄酮抗肿瘤作用的研究进展[J].国外医学卫生学分册,2001,28(2)：96-107.
[72]娄金丽,邱全瑛,何秀娟,等.威麦宁对小鼠Lewis肺癌细胞周期的影响[J].北京中医药大学学报,2004,38(2):67-69.
[73]金念祖,茅力,朱燕萍,等.槐米提取物对小鼠Lewis肺癌移植瘤细胞周期和PCNA表达的影响[J].中药新药与临床药理,2005,19(3):71-74.
[74]朱玲,王正荣,周黎明.异鼠李素及黄酮对人肺癌细胞A549人乳腺癌细胞MCF27的影响[J].四川生理科学杂志,2003,25(3):132.
[75]王光凤,王小晨,肖磷,等.柑橘黄酮川陈皮素的抗肿瘤作用研究[J].中草药,2007,38(11)：1694-1697.
[76]赵雪梅,朱大元,叶兴乾,等.柑桔属中类黄酮的研究进展[J].天然产物研究与开发,2002,14(1)：89-91.
[77]Mercedes.Oxidation of the Flavonol Quercetin by Polyphenol oxidase[J].J Agric Food Chem.1999,47(1):56-60.
[78]孙明瑜,左剑,段继峰.苦参总黄酮体内外抗肿瘤作用实验研究[J].中西医结合学报,2008,6(1)：51-59.
[79]Balasubramanian R,Narayanan M,Kedalgovindaram L. Cytotoxic activity of flavone glycoside from the stem of Indigofera aspalathoides Vahl[J].J Nat Med,2007,61(1): 80-831.
[80]Ko C H,Shen S C,Lee T J F,et al.Myricetin inhibits matrixmetalloproteinase 2 protein expression and enzyme activity in colorectal carcinoma cells[J].Mol Cancer Ther, 2005,4(2):281-290.
[81]Trochon V,Blot E,Cymbalista F,et al.Apigenin inhibits endothelial-cell proliferation in G(2)/M phase whereas it stimulates smooth-muscle cells by inhibiting p21 and p27 expression[J].Int J Cancer,2000,85(5):691-696.
[82]Kawaii S,Tomono Y,Katase E,et al.Effect of citrus flavonoids on HL-260 cell differentiation[J].Anticancer Res,1999,19(2A):1261-1269.
[83]黄冬生,陈金和.姜黄素诱导人肺癌细胞凋亡的作用机制初步研究[J].中国药理学通报,2003,19(8)：880-882.
[84]Banejee S,Manna S,Mukherjee S,et al.Black tea PolyPhenols restrict benzopyrene-induced mouse lung cancer progression through Inhibition of Cox-2 and induction of caspase-3 expression[J].Asian Pac J Cancer Prev,2006,7(4):661-666.
[85]Manna S K,Aggarwal R S,Sethi G.Morin(3,5,7,2',4'-Pentahydroxyflavone) abo-lishes nuclear factor-KB activation induced by various carcinogens and inflammatory stimuli,leading to suppression of nuclear factor-KB regulated gene expression and up-regulation of apoptosis[J].Clin Cancer Res,2007,13(7):2290-2297.
[86]Lee E,Enomoto R,Suzuki C,et al.Wogonin,a plant flavone,potentiates etoposide-induced apoptosis in cancer cells[J].Ann N Y Acad Sci,2007,1095(1):521-526.
[87]郑润辉,欧阳铭.肺癌转移机制的研究进展[J].国际内科学杂志,2007,34(8):445-448.
[88]毛海婷,张玲,王芸,等.淫羊藿甙对高转移肺癌细胞恶性表型的逆转作用及其控制机制的研究[J].中国肿瘤生物治疗杂志,1999,6(1):7.
[89]胡振,张惠斌,黄文龙.肿瘤多药耐药逆转剂的研究进展[J].药学进展,2002,26(3):129-133.
[90]Phang J,Poore C,Lopaczynska J,et al.Flavonol stimulated efflux of 7,12-dimethyl-benz(a)-anthracene in multidrugresistant breast cancer cells[J].Cancer Res,1993,53: 5977-5981.
[91]Guz N,Stermits F,Johnson J,et al.Flavonlignan and flavone inhibitors of a staphylo-coccus aureus multidrug resistance pump:structure-activity relationships[J].J Med Chem,2001,44:261-268.
[92]Versantvoort CH,Rhodes T,Twentyman PR. Acceleration of MRP-associated efflux of rhodamine 123 by genistein and related compounds[J].Br J Cancer,1996,74(12): 1949-1954.
[2]Parkin DM.Global cancer statistics in the year 2000[J].Cancet Oncol,2001,2(9):533-543.
[3]董志伟,乔友林,李连弟,等.中国癌症控制策略研究报告[J].中国肿瘤,2002,11(5):250-260.
[4]Mountain C F.Revisions in the international system for staging lung cancer[J].Chest, 1997,111:1710-1717.
[5]Kawai H,Kiura k,Tabata M,et al.Characterization of non-small-cell lung cancer cell lines established before and after chemotherapy[J].Lung Cancer,2002,35(3):305-314.
[6]Edelman M J,Gandara D R,Roachm R D,et al.Multimodality therapy in stage III non-small cell lung cancer[J].Ann Thorac Surg,1996,61 (5):1564-1572.
[7]Rosell,Gomez C J,Camps C,et al.Pieresectional chemotherapy in stage IIIA non-small-cell lung cancer:a 7 year assessment of a randomized controlled trial[J].Lung Cancer, 1999,26(1):7-14.
[8]Spasova I,Petera J,Hytych V.The role of neoadjuvant chemotherapy in marginally resectable or unresectable stage III non-small-cell lung cancer[J].Neoplasma,2002,49 (3):189-196.
[9]Non-small Cell Lung Cancer Collaborative Group.Chemotherapy in non-small cell lung cancer:a meta-analysis using updated individual patient data from 52 randomised clinical trials[J].Br Med. J,1995,311(7):899-909.
[10]中国医师协会胸外科医师分会.基于循证医学的肺癌诊断新进展[C].中国医师协会胸外科医师分会2008年年会论文集,2008:63-70.
[11]Kerr J F,W interford C M,Harmon B V.Apoptosis,its signi-ficance in cancer and cancer therapy [J].Cancer,1994,73(8):2013-2026.
[12]余晓,钱民章.HPLC法测定遵义产两种柑橘果皮中橙皮甙含量[J].遵义医学院学报,2005,28(2)：175-177.
[13]江纪武,肖庆祥.植物药有效成分手册[M].北京：人民卫生出版社,1986.561-562.
[14]Guardia T,Rotelli A E,Juarez A O,et al.Anti-inflammatory properties of plant flavonoids. Effects of rutin,quercetin and hesperidin on adjuvant arthritis in rat [J].IL Farmaco,2001,56(3):683-687.
[15]于辉,李春香,甘庆贤.陈皮的药理作用[J].生物磁学,2005,5(1):44-45.
[16]蓝航莲,孙树侠.柑橘类黄酮的生理活性和研究进展[J].中国食物与营养,2003(7):15-18.
[17]Tanaka T,Makita H,Ohnishi M,et al.Chemoprevention of 4-nitroquino line 1- oxide-induced oral carcinogenesis in rats by flavonoids diosmin and hesperidin,each alone and in combination[J].Cancer Res.1997,57(15):246-252.
[18]Tanaka T,Kohno H,Murakami M,et al.Suppression of azoxymethane-induced colon arcinogenesis in male F344 rats by mandarin juices rich in(3-crypt-oxanthin and hesperidin[J].Int. J.Cancer,2000,88:146-150.
[19]Keiko S,Yoshinobu H,Zheng Q,et al.Inhibition of inducible isoforms of cyclo-oxygen-ase and nitricoxide synthase by flavonoid hesperidin in mouse macrophage cell line[J]. Cancer Letters,2003,199(2):139-145.
[20]Park H J,Kim M J,Ha E,et al.Apoptotic effect of hesperidin through caspase 3 activ-ation in human colon cancer cells,SNU-C4[J].Phytomedicine,2008,15(1-2):147-51.
[21]Kim M J, Park H J,Hong M S,et al.Citrus reticulata Blanco induces apoptosis in human gastric cancer cells SNU-668[J].Nutr. Cancer,2005,51(18):78-82.
[22]张天泽,徐光炜.肿瘤学(上册).第二版[M].天津：天津科学技术出版社；沈阳：辽宁科学技术出版社,2005,842.
[23]鄂征.组织培养和分子细胞学技术[M].北京：科学出版社,1994.164-169.
[24]李曦,郭先健,黄桂君,等.人肺腺癌多药抗药细胞系LC23/CDDP细胞周期及DNA含量变化[J].河南肿瘤学杂志,1997,10(2):93-95.
[25]陈鹏,刘叙仪,赫复生.耐顺铂人肺腺癌细胞系A549/CDDP的建立及耐药机制[J].中国肿瘤临床,1995,3(4):582-587.
[26]张天泽,徐光炜.肿瘤学(上册).第二版[M].天津：天津科学技术出版社；沈阳：辽宁科学技术出版社,2005,210.
[27]顾后,贾勇.中药对肺癌细胞增殖与凋亡影响的研究进展[J].云南中医中药杂志,2007,28(5):42-44.
[28]孙玺媛,孙建立.益气养阴方逆转人肺腺癌A549/DDP多药耐药机理[J].实用肿瘤学杂志,2009,23(1)99:26-29.
[29]张天泽,徐光炜.肿瘤学(上册).第二版[M].天津：天津科学技术出版社；沈阳：辽宁科学技术出版社,2005,253.
[1]吴一龙,张明和,廖美琳,等.肺癌的诊断和分期临床指导[J].中国肺癌杂志,2003,6(5):330-334.
[2]杨宏健.天然药物化学[M].郑州：河南科学技术出版社,2007,83-89.
[3]叶任高,陆再英.内科学[M].北京：人民卫生出版社,2004:116-117.
[4]Kaufmann J A,Bickford P C,Taglialatela G.Free radical-dependent change in con-stitutive nuclear factor kappa B in the aged hippocampus[J].Neuroreport,2002,13(15): 1971-1978.
[5]陈国有,齐鹤,徐东花.黄酮类化合物的生物活性研究进展[J],黑龙江医药,2008,21(3):61-63.
[6]Stanisalw Burda,Wieslaw Oleszek.Antioxidant and antiradical activities of flavonoids [J],J A gric Food Chem,2001,49(6):274-279.
[7]Ha Sook Chung.Flavonoid constituents of chorizan the diffusa with potential cancer chemopreventive activity[J].J A gric Food Chem,1999,47(1):36-41.
[8]刘宏,赵金垣.自由基在理化因素致肺癌中的作用[J].环境与健康杂志,2008,25(1)：85-87.
[9]Mercedes.Oxidation of the flavonol quercetin by polyphenol oxidase[J].J Agric Food Chem.1999,47(1):56-60.
[10]张德权,台建祥,付勤,等.生物类黄酮的研究及应用概况[J].食品与发酵工业,1999,25(6)：52-56.
[11]Beate Baderschneider.Isolation and characterization of novel benzoates,cinnamates, flavonoids and lingmans from riesling wine and screening for antioxidant activity[J].J Agric Food Chem.2001,49(6):2788-2798.
[12]Rahman I,Biswas SK,Kirkham PA.Regulation inflammation and redox signaling by dietary polyphenols[J].Biochem Pharmacol,2006,72(11):1439-1452.
[13]王斌.食品中的免疫调节功能因子研究进展[J].氨基酸和生物资源,2009,31(1):70-73.
[14]Nanua S,Zick SM,Andrade JE,et al.Quercetin blocks airway epithelial cell chemokine expression[J].Am J Respir Cell Mol Biol,2006,35(5):602-610.
[15]唐嘉航,叶希韵,刘江,等.银杏叶总黄酮对胰岛素抵抗大鼠糖脂代谢和肝功能的影响[J].上海交通大学学报(医学版),2009,29(2)：150-154.
[16]Di Paola R,Mazzon E,Muia C,et al.Protective effect of HyPerieum perforatum in zymosan-induced multiple organ dysfunction syndrome:relationship to its in hibitory effect on nitric oxide production and its peroxynitrite scavenging activity[J].Nitrc Oxide,2007,16(1):118-130.
[17]Kumar P,Khanna M,Srivastava V,et al.Effect of quercetin supplementation on lung antioxidants after experimental influenza virus infection[J].Exp Lung Res,2005,31(5): 449-459.
[18]Giakoustidis AE,Giakoustidis DE,Iliadis S,et al.Attenuation of intestinal ischeia/re-perfudion induced liver and lung injury by intraperitoneal administration of (-)-epigallocatechin-3-gallate[J].Free Radic Res,2006,40(1):103-110.
[19]汪德清,房征宇,沈文梅,等.黄芪总黄酮抗紫外线损伤作用的实验研究[J].劳动医学,1998,5(4)：200-202.
[20]汪德清,沈文梅,田亚平,等.黄芪总黄酮对γ射线所致V79细胞DNA链断裂损伤防护作用的实验研究[J].中华放射医学与防护杂杂志,1995,1(2):106-107.
[21]齐琳,刘春宇,吴文倩,等.沙苑子黄酮对60Coγ射线损伤作用的影响[J].苏州大学学报(医学版),2008,28(1):26-29.
[22]金宏,刘丽,王先远,等.大豆异黄酮抗辐射作用的实验研究[J].氨基酸和生物资源,2004,26(3):23-26.
[23]孙维琦,郭英,袁小洁,等.大豆复合物对丫射线辐射损伤防护作用[J].中国公共卫生,2007,23(10)：1165-1166.
[24]张氽,阚建全.陈宗道生物类黄酮抗癌作用研究进展[J].中国野生植物资源,2003,22(4)：8-11.
[25]龙奇达,熊绍权,赵霞.槲皮素的癌化学预防和抗肿瘤作用研究进展[J].中华妇幼临床医学杂志,2008,4(4):56-59.
[26]高昕,王喜军.黄酮类化合物抗肿瘤作用研究进展[J].中医药信息,2005,22(5):33-34.
[27]黄华艺,查锡良.黄酮类化合物抗肿瘤作用研究进展[J].中国新药与临床杂,2002,21(7)：428-433.
[28]Balakrishnan A,Menon VP.Protective effect of hesperidin on nicotine induced toxicity in rats[J].Indian J Exp Biol,2007,45(2):194-202.
[29]Syed DN,Afaq F,Kweon MH,et al.Green to apolyphenol EGCG suppresses cigarette smoke condendate-induced NF-kappaB activation in normal human bronchial epith-elial cells[J].Oncogene,2007,26(5):673-682.
[30]邬海桥,周向.植物黄酮类的生物学特性及对呼吸系统疾病的影响[J].国际中医中药杂志,2007,29(4):223-226.
[31]Pang GG,Li ZH,Bai J,et al.Literature review of researches on physiological effects of Hesperidin[J].Nonwood Forest Res,2006,24 (4):83-86.
[32]卢波安,喜峰.中药抗肿瘤作用的研究[J].中国初级卫生保健,2008,22(9):72-73.
[33]秦善文,郑玉玲.抗肿瘤中药实验研究进展[J].河南中医,2005,25(2):76-78.
[34]赵金香,杨连玉,袁钠.大豆黄酮在畜牧生产中的研究及应用[J].吉林畜牧兽医,2003,4：4-6.
[35]胡成穆,陈琳,李荣,等.豹皮樟总黄酮对免疫低下小鼠免疫功能的影响[J].中国药理学通报,2007,23(6)：804-808.
[36]张莉,陈乃富,谷仿丽,等.蕨菜黄酮提取物免疫调节作用的实验研究[J].中国中医药科技,2009,16(1)：30-31.
[37]Saha P,Banerjee S,Ganguly C,et al.Black tea estract can modulate protein expression of H-ras,c-myc,p53,and Bcl-2 genes during pulmonary hyperplasia,dysplasia,dys-plasia, and carcinoma in situ[J].J Enciron Pathol Toxicol Oncol,2005,24(3):211-244.
[38]Yeh SL,Wu SH.Effects of quercetin on beta-apo-8-carotenal-induced DNA damage and cytochrome P1A2 expression in A549 cells[J].Chem Biol Interact,2006,163(3): 199-206.
[39]杨博,李志裕,尤启冬.黄酮类化合物的抗肿瘤作用机制研究进展[J].药学进展,2008,32(9)：391-397.
[40]李丽波,刘耕陶.硫氧还蛋白的生物学及其与阿尔茨海默病和帕金森病的关系[J].药学学报,2008,43(1)：1-8.
[41]Lu J,Papp L V,Fang J G,et al.Inhibition of mammalian thioredoxin reductase by some flavonoids:implications for myricetin and quercetin anticancer activity[J].Cancer Res, 2006,66(8):4410-4418.
[42]闫伟,吴波.DNA拓扑异构酶Ⅱ与细胞增殖[J].医学研究生学报,2004,17(6):535-538.
[43]王晨,张立实,何涛.染料木黄酮对体外细胞增殖的抑制作用研究[J].中国公卫生,2002,18(9)：1056-1058.
[44]杨小凤,雷海民,付宏征,等.栾树种子中黄酮类化学成分[J].药学学报,2000,35(3):208-211.
[45]Quintin J,Roullier C,Thoret C,et al.Synthesis and antitubulin evaluation of chromone-based analogues of combretastatins[J].Tetrahedron,2006,62(17):4038-4051.
[46]宋悦,沈铿.新型小分子细胞周期素抑制剂flavopiridol在肿瘤治疗中的应用[J].中华医学杂志,2005,85(12):862-864.
[47]Kalpana S,Maggie J,Rathos J.PravinMahajan:P276-00,a novel cyclindependent in-hibitor induces G1-G2 arrest,shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models [J].Mol Cancer Ther,2007,6(3):26-34.
[48]Sanchez-Martinez C,Shih C,Zhu G,et al.Studies on cyclindependent kinase inhibitors: indole-[2,3-a]pyrrolo[3,4-c]carbazoles versus bisindolylmalei-mides[J]. Bio org Med Chem Lett,2003,13(21):3841-3846.
[49]Kalpana S,Joshi.In vitro antitumor properties of a novel cyclindependent kinase in-hibitor,P276-00[J].Mol Cancer Ther,2007,6(3):918-982.
[50]朱婷,汪希鹏,马庆良.芳香化酶抑制剂治疗妇科恶性肿瘤进展[J].国际妇产科学杂志,2008,35(5):341-344.
[51]周向东,蔡文琴.芳香化酶mRNA在肺癌组织中表达的初步研究[J].中国肺癌杂志,2000,3(4)：269-271.
[52]周向东,蔡文琴,曹红卫.男性肺癌患者外周血性激素水平及其与肺癌组织中芳香化酶表达的相关性研究[J].癌症,2002,21(3):259-262.
[53]Ta N,Walle T.Aromatase inhibition by bioavailable methylated flavones[J].J Steroid Biochem Mol Biol,2007,107(122):127-129.
[54]苏莉莎,骆文龙.植物雌激素的作用[J].生命的化学,2006,26(1):58-59.
[55]马吉祥,李会庆.植物雌激素与肿瘤[J].国外医学肿瘤学分册,2001,28(6):416-420.
[56]周利红,李琦,唐中祥.中医药调控肿瘤信号转导的研究现状与思考[J].上海中医药大学学报,2008,22(6):77-81.
[57]邢雁霞,刘斌钰.受体型TPK-Ras-MAPK信号转导途径研究进展[J].大同医学专科学校学报,2006,26(1):42-43.
[58]陆涛,卢帅,李慧芳,等.肿瘤信号转导通路及相关药物研发的现状与展望(上)[J].中国药科大学学报,2008,39(3)：193-199.
[59]陆涛,卢帅,李慧芳,等.肿瘤信号转导通路及相关药物研发的现状与展望(下)[J].中国药科大学学报,2008,39(3)：289-300.
[60]LoPiccolo J,Granville CA,Gills JJ,et al.Targeting Akt in cancer therapy[J].Anticancer Drugs,2007,18(8):861-874.
[61]Zhang X,Jin B,Huang C.The PI3K/Akt pathway and its downstream transcriptional factors as targets for chemoprevention[J].Curr Cancer Drug Targets,2007,7(4):305-316.
[62]张百川,孟祥晨,张明江.表没食子儿茶素没食子酸酯对增殖性疾病生长因子的诱捕作用[J].中草药,2009,38(1):151-153.
[63]Kobayashi S,Shimamura T,Monti S,et al.Transcriptional profiling identifies cyelin D1 as a critical downstream effector of mutant epidermal growth factor receptor signal-ing[J].Cancer Res,2006,66(23):11389-11398.
[64]Nakahata N,Kyo R,Kutsuwa M,et al.Inhibition of mitogen-activated protein kinase cascade by baicalein,a flavonoid of natural origin[J].Nippon Yakurigaku Zasshi,1999, 114(Suppll):215-219.
[65]Hemstrom TH,Sandstrom M,Zhivotovsky B.Inhibitors of the PI3-kinase/Akt pathway induce mitotic catastrophe in non-smll cell lung cancer cells[J].Int J Cancer,2006, 119(5):1028-1038.
[66]Lee HY,Oh SH,Woo JK,et al.Chemopreventive effects of deguelin,a novel Akt in-hibitor,on tobacco-induced lung tumorigenesis[J].J Natl Cancer Inst,2005,97(22): 1695-1699.
[67]Lee YK,Isham CR,Kaufman SH,et al.Flavopiridol disrupts STAT3/DNA inter-actions,attenuates STAT3-directed transcription,and combines with the Jak kinase inhibitor AG490 to achieve cytotoxic synergy[J].Mol Cencer Ther,2006,5(1):138-148.
[68]Li Y,Ahmed F,Ali S,et al.Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemptherapeutic agents in human cancer cells[J].Cancer Res,2005,65(15):6934-6942.
[69]Ferrara N.Vascular endothelial growth factor as a target for anticancer therapy[J]. Oncologist,2004,9:2-10.
[70]Zhang Y Y,Shen S R.Inhibitory effects of tea catechins on tumor angiogenesis[J]. Chin J Cell Biol,2005,27(25):267-272.
[71]Nam S,Smith D M,Dou Q P.Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo[J].J Biol Chem,2001,276:13322-13330.
[72]施明.类黄酮抗肿瘤作用的研究进展[J].国外医学卫生学分册,2001,28(2)：96-107.
[72]娄金丽,邱全瑛,何秀娟,等.威麦宁对小鼠Lewis肺癌细胞周期的影响[J].北京中医药大学学报,2004,38(2):67-69.
[73]金念祖,茅力,朱燕萍,等.槐米提取物对小鼠Lewis肺癌移植瘤细胞周期和PCNA表达的影响[J].中药新药与临床药理,2005,19(3):71-74.
[74]朱玲,王正荣,周黎明.异鼠李素及黄酮对人肺癌细胞A549人乳腺癌细胞MCF27的影响[J].四川生理科学杂志,2003,25(3):132.
[75]王光凤,王小晨,肖磷,等.柑橘黄酮川陈皮素的抗肿瘤作用研究[J].中草药,2007,38(11)：1694-1697.
[76]赵雪梅,朱大元,叶兴乾,等.柑桔属中类黄酮的研究进展[J].天然产物研究与开发,2002,14(1)：89-91.
[77]Mercedes.Oxidation of the Flavonol Quercetin by Polyphenol oxidase[J].J Agric Food Chem.1999,47(1):56-60.
[78]孙明瑜,左剑,段继峰.苦参总黄酮体内外抗肿瘤作用实验研究[J].中西医结合学报,2008,6(1)：51-59.
[79]Balasubramanian R,Narayanan M,Kedalgovindaram L. Cytotoxic activity of flavone glycoside from the stem of Indigofera aspalathoides Vahl[J].J Nat Med,2007,61(1): 80-831.
[80]Ko C H,Shen S C,Lee T J F,et al.Myricetin inhibits matrixmetalloproteinase 2 protein expression and enzyme activity in colorectal carcinoma cells[J].Mol Cancer Ther, 2005,4(2):281-290.
[81]Trochon V,Blot E,Cymbalista F,et al.Apigenin inhibits endothelial-cell proliferation in G(2)/M phase whereas it stimulates smooth-muscle cells by inhibiting p21 and p27 expression[J].Int J Cancer,2000,85(5):691-696.
[82]Kawaii S,Tomono Y,Katase E,et al.Effect of citrus flavonoids on HL-260 cell differentiation[J].Anticancer Res,1999,19(2A):1261-1269.
[83]黄冬生,陈金和.姜黄素诱导人肺癌细胞凋亡的作用机制初步研究[J].中国药理学通报,2003,19(8)：880-882.
[84]Banejee S,Manna S,Mukherjee S,et al.Black tea PolyPhenols restrict benzopyrene-induced mouse lung cancer progression through Inhibition of Cox-2 and induction of caspase-3 expression[J].Asian Pac J Cancer Prev,2006,7(4):661-666.
[85]Manna S K,Aggarwal R S,Sethi G.Morin(3,5,7,2',4'-Pentahydroxyflavone) abo-lishes nuclear factor-KB activation induced by various carcinogens and inflammatory stimuli,leading to suppression of nuclear factor-KB regulated gene expression and up-regulation of apoptosis[J].Clin Cancer Res,2007,13(7):2290-2297.
[86]Lee E,Enomoto R,Suzuki C,et al.Wogonin,a plant flavone,potentiates etoposide-induced apoptosis in cancer cells[J].Ann N Y Acad Sci,2007,1095(1):521-526.
[87]郑润辉,欧阳铭.肺癌转移机制的研究进展[J].国际内科学杂志,2007,34(8):445-448.
[88]毛海婷,张玲,王芸,等.淫羊藿甙对高转移肺癌细胞恶性表型的逆转作用及其控制机制的研究[J].中国肿瘤生物治疗杂志,1999,6(1):7.
[89]胡振,张惠斌,黄文龙.肿瘤多药耐药逆转剂的研究进展[J].药学进展,2002,26(3):129-133.
[90]Phang J,Poore C,Lopaczynska J,et al.Flavonol stimulated efflux of 7,12-dimethyl-benz(a)-anthracene in multidrugresistant breast cancer cells[J].Cancer Res,1993,53: 5977-5981.
[91]Guz N,Stermits F,Johnson J,et al.Flavonlignan and flavone inhibitors of a staphylo-coccus aureus multidrug resistance pump:structure-activity relationships[J].J Med Chem,2001,44:261-268.
[92]Versantvoort CH,Rhodes T,Twentyman PR. Acceleration of MRP-associated efflux of rhodamine 123 by genistein and related compounds[J].Br J Cancer,1996,74(12): 1949-1954.