基于肿瘤特征的抗肿瘤中药药理学机制探析
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摘要
目的:基于肿瘤特征的抗肿瘤中药药理机制研究进展和有关研究标准化的问题。方法:检索PubMed,CNKI,重庆维普,百链云图书馆、读秀学术搜索网上数据库,针对肿瘤特征,将抗肿瘤中药药理学机制研究进行归纳总结。结果:基于肿瘤特征的抗肿瘤中药药理学机制研究可分为11大类:抗增殖信号维持、抗生长抑制逃避、增强免疫、抗无限复制、抗癌性促炎反应、抗侵袭转移、抗血管生成、抗基因组不稳定与突变、抗细胞死亡抵抗、抗细胞能量代谢失衡、抗肿瘤干细胞。结论与展望:基于肿瘤特征的抗肿瘤中药药理学机制分类方法有利于中药抗肿瘤的标准化研究,值得推广。并随着对肿瘤特征研究的深入,中药针对这些特征的研究必将随之发展。
Objective: To review the research progress of anticancer Chinese medicines(CMs) based on the hallmarks of cancer and discuss guideline for anticancer CMs. Methods: PubMed, CNKI, Chongqing VIP, Bailianyun Library, Duxiu Scholar online databases were retrieved. The mechanisms of CMs for anti-cancer were summarized. Results: The underlying mechanisms of Chinese medicines against cancer were divided into 11 categories by targeting: sustaining proliferative signaling, evading growth suppressor, avoiding immune destruction, enabling replicative immortality, tumorpromoting inflammation, activating invasion metastasis, inducing angiogenesis, genome instability & mutation, resisting cell death, deregulating cellular energetics, and cancer stem cells. Conclusion and Prospectives: The categories for CMs based on cancer hallmarks may facilitate the research standardization of CMs Pharmacology, which deserves further application. With the deepening of research on hallmarks of cancer, the research on these characteristics of Traditional Chinese Medicine will surely develop.
Objective: To review the research progress of anticancer Chinese medicines(CMs) based on the hallmarks of cancer and discuss guideline for anticancer CMs. Methods: PubMed, CNKI, Chongqing VIP, Bailianyun Library, Duxiu Scholar online databases were retrieved. The mechanisms of CMs for anti-cancer were summarized. Results: The underlying mechanisms of Chinese medicines against cancer were divided into 11 categories by targeting: sustaining proliferative signaling, evading growth suppressor, avoiding immune destruction, enabling replicative immortality, tumorpromoting inflammation, activating invasion metastasis, inducing angiogenesis, genome instability & mutation, resisting cell death, deregulating cellular energetics, and cancer stem cells. Conclusion and Prospectives: The categories for CMs based on cancer hallmarks may facilitate the research standardization of CMs Pharmacology, which deserves further application. With the deepening of research on hallmarks of cancer, the research on these characteristics of Traditional Chinese Medicine will surely develop.
引文
1孙梅艳,易敏春,李庆兰.中医古籍中对肿瘤病名及其病因病机的认识荟萃.中国卫生产业,2013,10(33):172-173.
2牛亚华,张青,杨国旺,等.中医古籍肿瘤术语研究的流程与方法探索.中医杂志,2015,56(9):745-748.
3吕玉萍,安丰辉,吕玉红,等.肿瘤中医病机各家杂谈.环球中医药,2010,3(3):225-226.
4徐成贺.中医古籍对肿瘤发病的多种因素研究.实用中医杂志,2005,19(4):299.
5 Bray F,Ferlay J,Soerjomataram I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36cancers in 185 countries.CA Cancer J Clin,2018,68(6):394-424.
6季宇彬.中药复方化学与药理(第一版).北京:人民卫生出版社,2013.
7周家驹,谢桂荣,严新建.中药抗癌活性成分(第一版).北京:科学出版社,2012.
8钱伯文.抗癌中药的临床应用(第一版).上海:上海翻译出版公司,1987.
9秦文星,臧远胜.抗癌必修课·乳腺癌.(第一版).上海:上海科学技术出版社,2015.
10金国梁,张勤.防癌抗癌中药(第一版).上海:上海科学技术出版社,2001.
11吴琪,李德民.中医药抗癌止痛新论(第一版).沈阳:辽宁科学技术出版社,1996.
12徐宏喜,冯奕斌,朱国福.抗肿瘤中药现代研究与临床应用(第一版).上海:上海科技出版社,2018.
13常敏毅.抗癌中药(第一版).长沙:湖北科学技术出版社,1996.
14章永红.抗癌中药大全(第一版).南京:江苏科学技术出版社,2000.
15古可珍.中药标准化问题及对策探讨.智库时代,2018,48:205.
16汪选斌.中药国际化与标准化研究问题的思考.湖北医药学院学报,2014,33(4):313-318.
17黄晓伟,安红梅,胡兵.现代解毒抗癌中药治疗大肠癌研究进展.环球中医药,2018,11(11):1838-1842.
18 Constantinidou A,Alifieris C,Trafalis D T.Targeting programmed cell death-1(PD-1)and Ligand(PD-L1):a new era in cancer active immunotherapy.Pharmacol Ther,2018.
19 Silva D A,Yu S,Ulge U Y,et al.De novo design of potent and selective mimics of IL-2 and IL-15.Nature,2019,565(7738):186-191.
20宋文静,冀慧雁,金若云,等.分子靶向肿瘤治疗研究现状.中国药物与临床,2018,18(11):1930-1933.
21 Hanahan D,Weinberg R A.Hallmarks of cancer:the next generation.Cell,2011,144(5):646-674.
22 Sherley J L.New cancer diagnostics and therapeutics from a ninth'hallmark of cancer':symmetric self-renewal by mutated distributed stem cells.Expert Rev Mol Diagn,2013,13(8):797-810.
23 Zou Y,Liu F Y,Wu J,et al.Mutational analysis of the RAS/RAF/MEK/ERK signaling pathway in 260 Han Chinese patients with cervical carcinoma.Oncol Lett,2017,14(2):2427-2431.
24 Hatashita M,Taniguchi M,Baba K,et al.Sinodielide A exerts thermosensitizing effects and induces apoptosis and G2/M cell cycle arrest in DU145 human prostate cancer cells via the Ras/Raf/MAPKand PI3K/Akt signaling pathways.Int J Mol Med,2014,33(2):406-414.
25 Jiang S,Ling C,Li W,et al.Molecular mechanisms of anti-cancer activities of beta-elemene:targeting hallmarks of cancer.Anticancer Agents Med Chem,2016,16(11):1426-1434.
26 Zhang X W,Yan X J,Zhou Z R,et al.Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML.Science,2010,328(5975):240-243.
27 Yang X B,Chai X S,Wu W Y,et al.Gefitinib plus Fuzheng Kang'ai Formula in patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutation:a randomized controlled trial.Chin J Integr Med,2018,24(10):734-740.
28 Xiong S Q,Li Y L,Wang S M,et al.Cohort study of EGFR-TKIs combined with traditional Chinese medicine and single EGFR-TKIs for advanced NSCLC(non(-)small cell lung cancer).Journal of Suchuan University(Medical Edition),2018,49(4):566-569.
29 Teng Y N,Wang Y,Hsu P L,et al.Mechanism of action of cytotoxic compounds from the seeds of Euphorbia lathyris.Phytomedicine,2018,41:62-66.
30 Chen L,Jiang Z,Ma H,et al.Volatile oil of acori graminei rhizomainduced apoptosis and autophagy are dependent on p53 status in human glioma cells.Sci Rep,2016,6:21148.
31 Wang Y,Yu H,Zhang J,et al.Anti-tumor effect of emodin on gynecological cancer cells.Cell Oncol(Dordr),2015,38(5):353-363.
32 Thacker P C,Karunagaran D.Curcumin and emodin down-regulate TGF-beta signaling pathway in human cervical cancer cells.PLoS One,2015,10(3):e0120045.
33 Dong X,Ni B,Fu J,et al.Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the mitochondrial caspasedependent pathway.Oncol Rep,2018,40(4):1985-1993.
34 Zhang K,Jiao K,Zhu Y,et al.Effect of emodin on proliferation and cell cycle of human oral squamous carcinoma Tca8113 cells in vitro.Journal of Southern Medical University,2015,35(5):665-670.
35 Suboj P,Babykutty S,Srinivas P,et al.Aloe emodin induces G2/M cell cycle arrest and apoptosis via activation of caspase-6 in human colon cancer cells.Pharmacology,2012,89(1-2):91-98.
36 Zhang J,Guo L,Zhang Q,et al.Aloe emodin suppresses EGF-induced neoplastic cell transformation by inhibiting the ERK/MSK1 and AKT/GSK3beta signaling pathways.Mol Med Rep,2018,18(6):5215-5220.
37 Jagadeeshan S,David D,Jisha S,et al.Solanum nigrum Unripe fruit fraction attenuates Adriamycin resistance by down-regulating multidrug resistance protein(Mdr)-1 through Jak-STAT pathway.BMCComplement Altern Med,2017,17(1):370.
38 Wang L M,Zhang M Y,Zhu Q S,et al.Hyperin enhances the sensitivity of hct8/vcr colon cancer cell line to vincristine by down-regulating pglycoprotein.Clin Lab,2018,64(3):269-275.
39 Huang B Y,Zeng Y,Li Y J,et al.Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance.Int J Oncol,2017,51(1):257-268.
40 Yuan Z T,Shi X J,Yuan Y X,et al.Bufalin reverses ABCB1-mediated drug resistance in colorectal cancer.Oncotarget,2017,8(29):48012-48026.
41 Tian Q T,Ding C Y,Song S S,et al.New tanshinone I derivatives S222and S439 similarly inhibit topoisomerase I/II but reveal different p53-dependency in inducing G2/M arrest and apoptosis.Biochem Pharmacol,2018,154:255-264.
42 Wang Z,Sun X,Feng Y,et al.Dihydromyricetin reverses MRP2-mediated MDR and enhances anticancer activity induced by oxaliplatin in colorectal cancer cells.Anticancer Drugs,2017,28(3):281-288.
43 Chen M C,Hsu H H,Chu Y Y,et al.Lupeol alters ER stress-signaling pathway by downregulating ABCG2 expression to induce Oxaliplatinresistant LoVo colorectal cancer cell apoptosis.Environ Toxicol,2018,33(5):587-593.
44 Sui H,Duan P,Guo P,et al.Zhi Zhen Fang formula reverses Hedgehog pathway mediated multidrug resistance in colorectal cancer.Oncol Rep,2017,38(4):2087-2095.
45 Zhong Z,Yu H,Wang S,et al.Anti-cancer effects of Rhizoma Curcumae against doxorubicin-resistant breast cancer cells.Chin Med,2018,13:44.
46 Zhao H D,Xie H J,Li J,et al.Research Progress on Reversing Multidrug Resistance in Tumors by Using Chinese Medicine.Chin JIntegr Med,2018,24(6):474-480.
47 Lin J.,Feng J.,Yang H.,et al.Scutellaria barbata D.Don inhibits 5-fluorouracil resistance in colorectal cancer by regulating PI3K/AKTpathway.Oncol Rep,2017,38(4):2293-2300.
48 Jin L,Xu M,Luo X H,et al.Stephania Tetrandra and Ginsengcontaining Chinese Herbal formulation nsenl reverses cisplatin resistance in lung cancer xenografts.Am J Chin Med,2017,45(2):385-401.
49 Galluzzi L,Vitale I,Abrams J M,et al.Molecular definitions of cell death subroutines:recommendations of the Nomenclature Committee on Cell Death 2012.Cell Death Differ,2012,19(1):107-120.
50 Sun K W,Ma Y Y,Guan T P,et al.Oridonin induces apoptosis in gastric cancer through Apaf-1,cytochrome c and caspase-3 signaling pathway.World J Gastroenterol,2012,18(48):7166-7174.
51 Cao C,Liu B,Zeng C,et al.A polymethoxyflavone from Laggera pterodonta induces apoptosis in imatinib-resistant K562R cells via activation of the intrinsic apoptosis pathway.Cancer Cell Int,2014,14(1):137.
52 Li H,Xiang L,Yang N,et al.Zhiheshouwu ethanol extract induces intrinsic apoptosis and reduces unsaturated fatty acids via SREBP1pathway in hepatocellular carcinoma cells.Food Chem Toxicol,2018,119:169-175.
53 Li W Y,Ng Y F,Zhang H,et al.Emodin elicits cytotoxicity in human lung adenocarcinoma A549 cells through inducing apoptosis.Inflammopharmacology,2014,22(2):127-134.
54关波,张松,郭舜,等.大黄素抑制胃癌细胞糖酵解并促进凋亡.现代生物医学进展,2018,18(13):2437-2441.
55 Wang X,Li L,Guan R,et al.Emodin Inhibits ATP-Induced Proliferation and Migration by Suppressing P2Y Receptors in Human Lung Adenocarcinoma Cells.Cell Physiol Biochem,2017,44(4):1337-1351.
56熊思敏,张金晓,康玮,等.大黄素诱导人肝癌HepG2细胞线粒体凋亡作用研究.药物评价研究,2018,41(5):773-779.
57 Lin Y,Chen W,Wang Z,et al.Emodin promotes the arrest of human lymphoma Raji cell proliferation through the UHRF1DNMT3ANp73pathways.Mol Med Rep,2017(5):6544-6551.
58 Zhong Z F,Yu H B,Wang C M,et al.Furanodiene induces extrinsic and intrinsic apoptosis in doxorubicin-resistant MCF-7 breast cancer cells via nf-kappab-independent mechanism.Front Pharmacol,2017,8:648.
59 Sun H,Huang M,Yao N,et al.The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells.Biochem Pharmacol,2017,146:87-100.
60周仕铁,王林,邵继春,等.度他雄胺和“扶正抑瘤”中药复方对人前列腺癌PC-3细胞转移抑制效应的对照研究.成都中医药大学学报,2015,38(2):10-15.
61 Hu B,An H M,Shen K P,et al.Modified Yi Guan Jian,a Chinese herbal formula,induces anoikis in Bel-7402 human hepatocarcinoma cells in vitro.Oncol Rep,2011.26(6):1465-1470.
62 Chen M,Guo Y,Zhao R,et al.Ophiopogonin B induces apoptosis,mitotic catastrophe and autophagy in A549 cells.Int J Oncol,2016,49(1):316-324.
63 Xu H Z,Huang Y,Wu Y L,et al.Pharicin A,a novel natural entkaurene diterpenoid,induces mitotic arrest and mitotic catastrophe of cancer cells by interfering with BubR1 function.Cell Cycle,2010,9(14):2897-907.
64 Xu W H,Li C H,Jiang T L.Ferroptosis pathway and its intervention regulated by Chinese materia medica.China Journal of Chinese Materia Medica,2018,43(20):4019-4026.
65马肖静,周慧婷,董熠,等.肿瘤发生与免疫逃逸相关机制的研究进展.肿瘤学杂志,2018,24(11):1046-1050.
66赵瑞宝,曹慧慧,张瑞卿,等.大黄?虫丸对Lewis肺癌小鼠免疫状态的影响.陕西中医学院学报,2016,17(3):13-16.
67吕庆亮,孙长岗,庄静,等.肺积1号方对荷瘤小鼠淋巴细胞亚群的影响.中医药导报,2014,20(8):25-28.
68王磊,高月求,周荣耀.补肾健脾方对HBeAg阳性原发性肝癌伴肝硬化患者免疫功能和生存质量影响.辽宁中医杂志,2015,42(2):249-253.
69宋卿,季青,李琦.中医药调节肿瘤免疫的临床及机制研究.中华中医药杂志,2018,33(10):542-545.
70唐珍,王含彦,郭冬梅.端粒(酶)对衰老及肿瘤的调节研究进展.中国现代医学杂志,2018,28(30):43-49.
71袁富文,童坦军.细胞衰老与肿瘤治疗.生物化学与生物物理进展,2018,45(5):494-500.
72胡兵,安红梅,沈克平,等.藤龙补中汤促结肠癌LS-174-T细胞衰老及其机制.中西医结合学报,2010,8(11):1048-1052.
73 Dong A,Fang Y,Zhang L,et al.Caffeic acid 3,4-dihydroxy-phenethyl ester induces cancer cell senescence by suppressing twist expression.The Journal of pharmacology and experimental therapeutics,2011,339(1):238-247.
74 Zu C,Qin G,Yang C,et al.Low dose Emodin induces tumor senescence for boosting breast cancer chemotherapy via silencing NRARP.Biochem Biophys Res Commun,2018,505(4):973-978.
75高丰厚,郭竹英,徐芒华,等.冬凌草甲素诱导结直肠癌细胞SW-1116凋亡与衰老的体内外实验研究.上海交通大学学报(医学版),2010,30(6):683-688.
76林骏,白晓春.mTOR信号通路与“炎-癌”转变.生物化学与生物物理进展,2014,41(1):79-86.
77袁嘉嘉,孙志广.论“炎-癌转化”的中医病因病机.吉林中医药,2016,36(01):5-8.
78 Nikzad-Langerodi R,Ortmann S,Pferschy-Wenzig E M,et al.Assessment of anti-inflammatory properties of extracts from Honeysuckle(Lonicera sp.L.,Caprifoliaceae)by ATR-FTIR spectroscopy.Talanta,2017,175:264-272.
79贾晓娟.6-姜烯酚对人卵巢癌SKOV-3和A2780细胞生长和促炎因子表达的抑制作用.成都:成都中医药大学硕士研究生学位论文,2015.
80 Tang Y M,Cao Q Y,Guo X Y,et al.Inhibition of p38 and ERK1/2pathways by Sparstolonin B suppresses inflammation-induced melanoma metastasis.Biomed Pharmacother,2017,98:382.
81王艳春,王雪梅,孙严洁,等.化瘀解毒方对胃癌大鼠血清炎症因子、免疫功能和肿瘤相关因子的影响.中医学报,2017,32(6):905-908.
82于奇,冯海.小檗碱抗肿瘤机制研究.哈尔滨医科大学学报,2018,52(3):306-309.
83 Wang X,Wang N,Li H,et al.Up-Regulation of PAI-1 and down-regulation of uPA are involved in suppression of invasiveness and motility of hepatocellular carcinoma cells by a natural compound berberine.Int JMol Sci,2016,17(4):577.
84 Fang C Y,Wu C Z,Chen P N,et al.Antimetastatic potentials of salvianolic acid A on oral squamous cell carcinoma by targeting MMP-2and the c-Raf/MEK/ERK pathway.Environ Toxicol,2018,33(5):545-554.
85 Tan H Y,Wang N,Li S,et al.Repression of WT1-Mediated LEF1transcription by mangiferin governs beta-catenin-independent wnt signalling inactivation in hepatocellular carcinoma.Cell Physiol Biochem,2018,47(5):1819-1834.
86 Cheng C S,Chen J,Tan H Y,et al.Scutellaria baicalensis and cancer treatment:recent progress and perspectives in biomedical and clinical studies.Am J Chin Med,2018,46(1):25-54.
87杨念,向龙超,曹风军,等.大黄素对肿瘤转移作用及机制的研究进展.肿瘤药学,2016,6(3):173-177.
88 Shiau A L,Shen Y T,Hsieh J L,et al.Scutellaria barbata inhibits angiogenesis through downregulation of HIF-1 alpha in lung tumor.Environ Toxicol,2014,29(4):363-370.
89 Yang J,Yang G,Hou G,et al.Scutellaria barbata D.Don polysaccharides inhibit the growth of Calu-3 xenograft tumors via suppression of the HER2 pathway and angiogenesis.Oncol Lett,2015,9(6):2721-2725.
90 Zeng J,Yan R,Pan H,v.Weipixiao attenuate early angiogenesis in rats with gastric precancerous lesions.BMC Complement Altern Med,2018,18(1):250.
91 Li L J,Xu N W,Gao R L,et al.Effects of Danshen Injection on inhibiting proliferation and inducing apoptosis through down-regulation of mutant JAK2 gene and its protein phosphorylation in human erythroid leukemic cells.Chin J Integr Med,2014,20(5):381-386.
92 Han S Y,Zhao W,Sun H,et al.Marsdenia tenacissima extract enhances gefitinib efficacy in non-small cell lung cancer xenografts.Phytomedicine,2015,22(5):560-567.
93 Guerram M,Jiang Z Z,Yousef B A,et al.The potential utility of acetyltanshinone IIA in the treatment of HER2-overexpressed breast cancer:Induction of cancer cell death by targeting apoptotic and metabolic signaling pathways.Oncotarget,2015,6(26):21865-21877.
94 Bing Z,Cheng Z,Shi D,et al.Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology.BMC Complement Altern Med,2018,18(1):293.
95 Li F F,Yi S,Wen L,et al.Oridonin induces NPM mutant protein translocation and apoptosis in NPM1c+acute myeloid leukemia cells in vitro.Acta Pharmacol Sin,2014,35(6):806-813.
96吴彤,骆严.糖代谢重编程与肿瘤生长.生命的化学,2018,38(3):383-388.
97雷婉婷,王静萱.肿瘤微环境在肿瘤细胞有氧糖酵解中的作用.实用肿瘤学杂志,2018,32(2):189-192.
98 Guo W,Tan H Y,Wang N,et al.Deciphering hepatocellular carcinoma through metabolomics:from biomarker discovery to therapy evaluation.Cancer Manag Res,2018,10:715-734.
99 Lin L L,Hsia C R,Hsu C L,et al.Integrating transcriptomics and proteomics to show that tanshinone IIA suppresses cell growth by blocking glucose metabolism in gastric cancer cells.BMC Genomics,2015,16:41.
100袁玉梅.胃痞消对胃癌前病变大鼠胃黏膜有氧糖酵解的调控机制.广州:广州中医药大学硕士研究生学位论文,2014.
101杨念,曹风军,霍剑伟,等.基于SREBP1的制何首乌抗肝癌脂代谢蒽醌类活性成分的筛选.湖北医药学院学报,2018,37(2):156-160.
102 Cho Y R,Lee J H,Kim J H,et al.Matrine suppresses KRAS-driven pancreatic cancer growth by inhibiting autophagy-mediated energy metabolism.Mol Oncol,2018,12(7):1203-1215.
103 Kim J,Lee J S,Jung J,et al.Emodin suppresses maintenance of stemness by augmenting proteosomal degradation of epidermal growth factor receptor/epidermal growth factor receptor variant III in glioma stem cells.Stem Cells Dev,2015,24(3):284-295.
104 Li X X,Dong Y,Wang W,et al.Emodin as an effective agent in targeting cancer stem-like side population cells of gallbladder carcinoma.Stem Cells Dev,2013,22(4):554-66.
105 Hong M,Tan H Y,Li S,et al.Cancer stem cells:the potential targets of chinese medicines and their active compounds.Int J Mol Sci,2016,17(6):893.
106 Hanahan D,Weinberg R A.The hallmarks of cancer.Cell,2000,100(1):57-70.
107马守宝,林丹丹,刘海燕.炎症细胞因子在肿瘤微环境中的作用及其作为治疗靶点的研究进展.生命科学,2016,28(2):182-191.
2牛亚华,张青,杨国旺,等.中医古籍肿瘤术语研究的流程与方法探索.中医杂志,2015,56(9):745-748.
3吕玉萍,安丰辉,吕玉红,等.肿瘤中医病机各家杂谈.环球中医药,2010,3(3):225-226.
4徐成贺.中医古籍对肿瘤发病的多种因素研究.实用中医杂志,2005,19(4):299.
5 Bray F,Ferlay J,Soerjomataram I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36cancers in 185 countries.CA Cancer J Clin,2018,68(6):394-424.
6季宇彬.中药复方化学与药理(第一版).北京:人民卫生出版社,2013.
7周家驹,谢桂荣,严新建.中药抗癌活性成分(第一版).北京:科学出版社,2012.
8钱伯文.抗癌中药的临床应用(第一版).上海:上海翻译出版公司,1987.
9秦文星,臧远胜.抗癌必修课·乳腺癌.(第一版).上海:上海科学技术出版社,2015.
10金国梁,张勤.防癌抗癌中药(第一版).上海:上海科学技术出版社,2001.
11吴琪,李德民.中医药抗癌止痛新论(第一版).沈阳:辽宁科学技术出版社,1996.
12徐宏喜,冯奕斌,朱国福.抗肿瘤中药现代研究与临床应用(第一版).上海:上海科技出版社,2018.
13常敏毅.抗癌中药(第一版).长沙:湖北科学技术出版社,1996.
14章永红.抗癌中药大全(第一版).南京:江苏科学技术出版社,2000.
15古可珍.中药标准化问题及对策探讨.智库时代,2018,48:205.
16汪选斌.中药国际化与标准化研究问题的思考.湖北医药学院学报,2014,33(4):313-318.
17黄晓伟,安红梅,胡兵.现代解毒抗癌中药治疗大肠癌研究进展.环球中医药,2018,11(11):1838-1842.
18 Constantinidou A,Alifieris C,Trafalis D T.Targeting programmed cell death-1(PD-1)and Ligand(PD-L1):a new era in cancer active immunotherapy.Pharmacol Ther,2018.
19 Silva D A,Yu S,Ulge U Y,et al.De novo design of potent and selective mimics of IL-2 and IL-15.Nature,2019,565(7738):186-191.
20宋文静,冀慧雁,金若云,等.分子靶向肿瘤治疗研究现状.中国药物与临床,2018,18(11):1930-1933.
21 Hanahan D,Weinberg R A.Hallmarks of cancer:the next generation.Cell,2011,144(5):646-674.
22 Sherley J L.New cancer diagnostics and therapeutics from a ninth'hallmark of cancer':symmetric self-renewal by mutated distributed stem cells.Expert Rev Mol Diagn,2013,13(8):797-810.
23 Zou Y,Liu F Y,Wu J,et al.Mutational analysis of the RAS/RAF/MEK/ERK signaling pathway in 260 Han Chinese patients with cervical carcinoma.Oncol Lett,2017,14(2):2427-2431.
24 Hatashita M,Taniguchi M,Baba K,et al.Sinodielide A exerts thermosensitizing effects and induces apoptosis and G2/M cell cycle arrest in DU145 human prostate cancer cells via the Ras/Raf/MAPKand PI3K/Akt signaling pathways.Int J Mol Med,2014,33(2):406-414.
25 Jiang S,Ling C,Li W,et al.Molecular mechanisms of anti-cancer activities of beta-elemene:targeting hallmarks of cancer.Anticancer Agents Med Chem,2016,16(11):1426-1434.
26 Zhang X W,Yan X J,Zhou Z R,et al.Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML.Science,2010,328(5975):240-243.
27 Yang X B,Chai X S,Wu W Y,et al.Gefitinib plus Fuzheng Kang'ai Formula in patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutation:a randomized controlled trial.Chin J Integr Med,2018,24(10):734-740.
28 Xiong S Q,Li Y L,Wang S M,et al.Cohort study of EGFR-TKIs combined with traditional Chinese medicine and single EGFR-TKIs for advanced NSCLC(non(-)small cell lung cancer).Journal of Suchuan University(Medical Edition),2018,49(4):566-569.
29 Teng Y N,Wang Y,Hsu P L,et al.Mechanism of action of cytotoxic compounds from the seeds of Euphorbia lathyris.Phytomedicine,2018,41:62-66.
30 Chen L,Jiang Z,Ma H,et al.Volatile oil of acori graminei rhizomainduced apoptosis and autophagy are dependent on p53 status in human glioma cells.Sci Rep,2016,6:21148.
31 Wang Y,Yu H,Zhang J,et al.Anti-tumor effect of emodin on gynecological cancer cells.Cell Oncol(Dordr),2015,38(5):353-363.
32 Thacker P C,Karunagaran D.Curcumin and emodin down-regulate TGF-beta signaling pathway in human cervical cancer cells.PLoS One,2015,10(3):e0120045.
33 Dong X,Ni B,Fu J,et al.Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the mitochondrial caspasedependent pathway.Oncol Rep,2018,40(4):1985-1993.
34 Zhang K,Jiao K,Zhu Y,et al.Effect of emodin on proliferation and cell cycle of human oral squamous carcinoma Tca8113 cells in vitro.Journal of Southern Medical University,2015,35(5):665-670.
35 Suboj P,Babykutty S,Srinivas P,et al.Aloe emodin induces G2/M cell cycle arrest and apoptosis via activation of caspase-6 in human colon cancer cells.Pharmacology,2012,89(1-2):91-98.
36 Zhang J,Guo L,Zhang Q,et al.Aloe emodin suppresses EGF-induced neoplastic cell transformation by inhibiting the ERK/MSK1 and AKT/GSK3beta signaling pathways.Mol Med Rep,2018,18(6):5215-5220.
37 Jagadeeshan S,David D,Jisha S,et al.Solanum nigrum Unripe fruit fraction attenuates Adriamycin resistance by down-regulating multidrug resistance protein(Mdr)-1 through Jak-STAT pathway.BMCComplement Altern Med,2017,17(1):370.
38 Wang L M,Zhang M Y,Zhu Q S,et al.Hyperin enhances the sensitivity of hct8/vcr colon cancer cell line to vincristine by down-regulating pglycoprotein.Clin Lab,2018,64(3):269-275.
39 Huang B Y,Zeng Y,Li Y J,et al.Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance.Int J Oncol,2017,51(1):257-268.
40 Yuan Z T,Shi X J,Yuan Y X,et al.Bufalin reverses ABCB1-mediated drug resistance in colorectal cancer.Oncotarget,2017,8(29):48012-48026.
41 Tian Q T,Ding C Y,Song S S,et al.New tanshinone I derivatives S222and S439 similarly inhibit topoisomerase I/II but reveal different p53-dependency in inducing G2/M arrest and apoptosis.Biochem Pharmacol,2018,154:255-264.
42 Wang Z,Sun X,Feng Y,et al.Dihydromyricetin reverses MRP2-mediated MDR and enhances anticancer activity induced by oxaliplatin in colorectal cancer cells.Anticancer Drugs,2017,28(3):281-288.
43 Chen M C,Hsu H H,Chu Y Y,et al.Lupeol alters ER stress-signaling pathway by downregulating ABCG2 expression to induce Oxaliplatinresistant LoVo colorectal cancer cell apoptosis.Environ Toxicol,2018,33(5):587-593.
44 Sui H,Duan P,Guo P,et al.Zhi Zhen Fang formula reverses Hedgehog pathway mediated multidrug resistance in colorectal cancer.Oncol Rep,2017,38(4):2087-2095.
45 Zhong Z,Yu H,Wang S,et al.Anti-cancer effects of Rhizoma Curcumae against doxorubicin-resistant breast cancer cells.Chin Med,2018,13:44.
46 Zhao H D,Xie H J,Li J,et al.Research Progress on Reversing Multidrug Resistance in Tumors by Using Chinese Medicine.Chin JIntegr Med,2018,24(6):474-480.
47 Lin J.,Feng J.,Yang H.,et al.Scutellaria barbata D.Don inhibits 5-fluorouracil resistance in colorectal cancer by regulating PI3K/AKTpathway.Oncol Rep,2017,38(4):2293-2300.
48 Jin L,Xu M,Luo X H,et al.Stephania Tetrandra and Ginsengcontaining Chinese Herbal formulation nsenl reverses cisplatin resistance in lung cancer xenografts.Am J Chin Med,2017,45(2):385-401.
49 Galluzzi L,Vitale I,Abrams J M,et al.Molecular definitions of cell death subroutines:recommendations of the Nomenclature Committee on Cell Death 2012.Cell Death Differ,2012,19(1):107-120.
50 Sun K W,Ma Y Y,Guan T P,et al.Oridonin induces apoptosis in gastric cancer through Apaf-1,cytochrome c and caspase-3 signaling pathway.World J Gastroenterol,2012,18(48):7166-7174.
51 Cao C,Liu B,Zeng C,et al.A polymethoxyflavone from Laggera pterodonta induces apoptosis in imatinib-resistant K562R cells via activation of the intrinsic apoptosis pathway.Cancer Cell Int,2014,14(1):137.
52 Li H,Xiang L,Yang N,et al.Zhiheshouwu ethanol extract induces intrinsic apoptosis and reduces unsaturated fatty acids via SREBP1pathway in hepatocellular carcinoma cells.Food Chem Toxicol,2018,119:169-175.
53 Li W Y,Ng Y F,Zhang H,et al.Emodin elicits cytotoxicity in human lung adenocarcinoma A549 cells through inducing apoptosis.Inflammopharmacology,2014,22(2):127-134.
54关波,张松,郭舜,等.大黄素抑制胃癌细胞糖酵解并促进凋亡.现代生物医学进展,2018,18(13):2437-2441.
55 Wang X,Li L,Guan R,et al.Emodin Inhibits ATP-Induced Proliferation and Migration by Suppressing P2Y Receptors in Human Lung Adenocarcinoma Cells.Cell Physiol Biochem,2017,44(4):1337-1351.
56熊思敏,张金晓,康玮,等.大黄素诱导人肝癌HepG2细胞线粒体凋亡作用研究.药物评价研究,2018,41(5):773-779.
57 Lin Y,Chen W,Wang Z,et al.Emodin promotes the arrest of human lymphoma Raji cell proliferation through the UHRF1DNMT3ANp73pathways.Mol Med Rep,2017(5):6544-6551.
58 Zhong Z F,Yu H B,Wang C M,et al.Furanodiene induces extrinsic and intrinsic apoptosis in doxorubicin-resistant MCF-7 breast cancer cells via nf-kappab-independent mechanism.Front Pharmacol,2017,8:648.
59 Sun H,Huang M,Yao N,et al.The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells.Biochem Pharmacol,2017,146:87-100.
60周仕铁,王林,邵继春,等.度他雄胺和“扶正抑瘤”中药复方对人前列腺癌PC-3细胞转移抑制效应的对照研究.成都中医药大学学报,2015,38(2):10-15.
61 Hu B,An H M,Shen K P,et al.Modified Yi Guan Jian,a Chinese herbal formula,induces anoikis in Bel-7402 human hepatocarcinoma cells in vitro.Oncol Rep,2011.26(6):1465-1470.
62 Chen M,Guo Y,Zhao R,et al.Ophiopogonin B induces apoptosis,mitotic catastrophe and autophagy in A549 cells.Int J Oncol,2016,49(1):316-324.
63 Xu H Z,Huang Y,Wu Y L,et al.Pharicin A,a novel natural entkaurene diterpenoid,induces mitotic arrest and mitotic catastrophe of cancer cells by interfering with BubR1 function.Cell Cycle,2010,9(14):2897-907.
64 Xu W H,Li C H,Jiang T L.Ferroptosis pathway and its intervention regulated by Chinese materia medica.China Journal of Chinese Materia Medica,2018,43(20):4019-4026.
65马肖静,周慧婷,董熠,等.肿瘤发生与免疫逃逸相关机制的研究进展.肿瘤学杂志,2018,24(11):1046-1050.
66赵瑞宝,曹慧慧,张瑞卿,等.大黄?虫丸对Lewis肺癌小鼠免疫状态的影响.陕西中医学院学报,2016,17(3):13-16.
67吕庆亮,孙长岗,庄静,等.肺积1号方对荷瘤小鼠淋巴细胞亚群的影响.中医药导报,2014,20(8):25-28.
68王磊,高月求,周荣耀.补肾健脾方对HBeAg阳性原发性肝癌伴肝硬化患者免疫功能和生存质量影响.辽宁中医杂志,2015,42(2):249-253.
69宋卿,季青,李琦.中医药调节肿瘤免疫的临床及机制研究.中华中医药杂志,2018,33(10):542-545.
70唐珍,王含彦,郭冬梅.端粒(酶)对衰老及肿瘤的调节研究进展.中国现代医学杂志,2018,28(30):43-49.
71袁富文,童坦军.细胞衰老与肿瘤治疗.生物化学与生物物理进展,2018,45(5):494-500.
72胡兵,安红梅,沈克平,等.藤龙补中汤促结肠癌LS-174-T细胞衰老及其机制.中西医结合学报,2010,8(11):1048-1052.
73 Dong A,Fang Y,Zhang L,et al.Caffeic acid 3,4-dihydroxy-phenethyl ester induces cancer cell senescence by suppressing twist expression.The Journal of pharmacology and experimental therapeutics,2011,339(1):238-247.
74 Zu C,Qin G,Yang C,et al.Low dose Emodin induces tumor senescence for boosting breast cancer chemotherapy via silencing NRARP.Biochem Biophys Res Commun,2018,505(4):973-978.
75高丰厚,郭竹英,徐芒华,等.冬凌草甲素诱导结直肠癌细胞SW-1116凋亡与衰老的体内外实验研究.上海交通大学学报(医学版),2010,30(6):683-688.
76林骏,白晓春.mTOR信号通路与“炎-癌”转变.生物化学与生物物理进展,2014,41(1):79-86.
77袁嘉嘉,孙志广.论“炎-癌转化”的中医病因病机.吉林中医药,2016,36(01):5-8.
78 Nikzad-Langerodi R,Ortmann S,Pferschy-Wenzig E M,et al.Assessment of anti-inflammatory properties of extracts from Honeysuckle(Lonicera sp.L.,Caprifoliaceae)by ATR-FTIR spectroscopy.Talanta,2017,175:264-272.
79贾晓娟.6-姜烯酚对人卵巢癌SKOV-3和A2780细胞生长和促炎因子表达的抑制作用.成都:成都中医药大学硕士研究生学位论文,2015.
80 Tang Y M,Cao Q Y,Guo X Y,et al.Inhibition of p38 and ERK1/2pathways by Sparstolonin B suppresses inflammation-induced melanoma metastasis.Biomed Pharmacother,2017,98:382.
81王艳春,王雪梅,孙严洁,等.化瘀解毒方对胃癌大鼠血清炎症因子、免疫功能和肿瘤相关因子的影响.中医学报,2017,32(6):905-908.
82于奇,冯海.小檗碱抗肿瘤机制研究.哈尔滨医科大学学报,2018,52(3):306-309.
83 Wang X,Wang N,Li H,et al.Up-Regulation of PAI-1 and down-regulation of uPA are involved in suppression of invasiveness and motility of hepatocellular carcinoma cells by a natural compound berberine.Int JMol Sci,2016,17(4):577.
84 Fang C Y,Wu C Z,Chen P N,et al.Antimetastatic potentials of salvianolic acid A on oral squamous cell carcinoma by targeting MMP-2and the c-Raf/MEK/ERK pathway.Environ Toxicol,2018,33(5):545-554.
85 Tan H Y,Wang N,Li S,et al.Repression of WT1-Mediated LEF1transcription by mangiferin governs beta-catenin-independent wnt signalling inactivation in hepatocellular carcinoma.Cell Physiol Biochem,2018,47(5):1819-1834.
86 Cheng C S,Chen J,Tan H Y,et al.Scutellaria baicalensis and cancer treatment:recent progress and perspectives in biomedical and clinical studies.Am J Chin Med,2018,46(1):25-54.
87杨念,向龙超,曹风军,等.大黄素对肿瘤转移作用及机制的研究进展.肿瘤药学,2016,6(3):173-177.
88 Shiau A L,Shen Y T,Hsieh J L,et al.Scutellaria barbata inhibits angiogenesis through downregulation of HIF-1 alpha in lung tumor.Environ Toxicol,2014,29(4):363-370.
89 Yang J,Yang G,Hou G,et al.Scutellaria barbata D.Don polysaccharides inhibit the growth of Calu-3 xenograft tumors via suppression of the HER2 pathway and angiogenesis.Oncol Lett,2015,9(6):2721-2725.
90 Zeng J,Yan R,Pan H,v.Weipixiao attenuate early angiogenesis in rats with gastric precancerous lesions.BMC Complement Altern Med,2018,18(1):250.
91 Li L J,Xu N W,Gao R L,et al.Effects of Danshen Injection on inhibiting proliferation and inducing apoptosis through down-regulation of mutant JAK2 gene and its protein phosphorylation in human erythroid leukemic cells.Chin J Integr Med,2014,20(5):381-386.
92 Han S Y,Zhao W,Sun H,et al.Marsdenia tenacissima extract enhances gefitinib efficacy in non-small cell lung cancer xenografts.Phytomedicine,2015,22(5):560-567.
93 Guerram M,Jiang Z Z,Yousef B A,et al.The potential utility of acetyltanshinone IIA in the treatment of HER2-overexpressed breast cancer:Induction of cancer cell death by targeting apoptotic and metabolic signaling pathways.Oncotarget,2015,6(26):21865-21877.
94 Bing Z,Cheng Z,Shi D,et al.Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology.BMC Complement Altern Med,2018,18(1):293.
95 Li F F,Yi S,Wen L,et al.Oridonin induces NPM mutant protein translocation and apoptosis in NPM1c+acute myeloid leukemia cells in vitro.Acta Pharmacol Sin,2014,35(6):806-813.
96吴彤,骆严.糖代谢重编程与肿瘤生长.生命的化学,2018,38(3):383-388.
97雷婉婷,王静萱.肿瘤微环境在肿瘤细胞有氧糖酵解中的作用.实用肿瘤学杂志,2018,32(2):189-192.
98 Guo W,Tan H Y,Wang N,et al.Deciphering hepatocellular carcinoma through metabolomics:from biomarker discovery to therapy evaluation.Cancer Manag Res,2018,10:715-734.
99 Lin L L,Hsia C R,Hsu C L,et al.Integrating transcriptomics and proteomics to show that tanshinone IIA suppresses cell growth by blocking glucose metabolism in gastric cancer cells.BMC Genomics,2015,16:41.
100袁玉梅.胃痞消对胃癌前病变大鼠胃黏膜有氧糖酵解的调控机制.广州:广州中医药大学硕士研究生学位论文,2014.
101杨念,曹风军,霍剑伟,等.基于SREBP1的制何首乌抗肝癌脂代谢蒽醌类活性成分的筛选.湖北医药学院学报,2018,37(2):156-160.
102 Cho Y R,Lee J H,Kim J H,et al.Matrine suppresses KRAS-driven pancreatic cancer growth by inhibiting autophagy-mediated energy metabolism.Mol Oncol,2018,12(7):1203-1215.
103 Kim J,Lee J S,Jung J,et al.Emodin suppresses maintenance of stemness by augmenting proteosomal degradation of epidermal growth factor receptor/epidermal growth factor receptor variant III in glioma stem cells.Stem Cells Dev,2015,24(3):284-295.
104 Li X X,Dong Y,Wang W,et al.Emodin as an effective agent in targeting cancer stem-like side population cells of gallbladder carcinoma.Stem Cells Dev,2013,22(4):554-66.
105 Hong M,Tan H Y,Li S,et al.Cancer stem cells:the potential targets of chinese medicines and their active compounds.Int J Mol Sci,2016,17(6):893.
106 Hanahan D,Weinberg R A.The hallmarks of cancer.Cell,2000,100(1):57-70.
107马守宝,林丹丹,刘海燕.炎症细胞因子在肿瘤微环境中的作用及其作为治疗靶点的研究进展.生命科学,2016,28(2):182-191.