二甲双胍的抗肿瘤作用

doi:10.3760/cma.j.issn.1673-422X.2015.04.011

摘要/Abstract

摘要： 二甲双胍作为一种廉价安全高效的糖尿病药物已应用多年，近年来研究显示其对各种肿瘤细胞都有不同程度的抑制作用。二甲双胍的抗肿瘤机制尚未完全明确，可能与糖代谢及蛋白激酶途径有关，也可能与炎症因子介导肿瘤杀伤有关。二甲双胍对不同肿瘤细胞杀伤效果不同，对其他抗肿瘤治疗也有一些辅助作用。

关键词: 二甲双胍, 肿瘤, 抗肿瘤

Abstract: Metformin as a cheap, safe and effective diabetes drug， has been used for many years. Recently, many studies have shown its variety inhibition of tumor cells. Its antitumor mechanism is not entirely clear; may be related to glucose metabolism and protein kinase or inflammatory cytokines mediating tumor killing. Metformin has different cytotoxic effects to various tumor cell, as well as playing some auxiliary roles on other antitumor methods.

Key words: Metformin, Neoplasms, Antitumor

郭延勋；马士崟. 二甲双胍的抗肿瘤作用[J]. 国际肿瘤学杂志, 2015, 42(4): 281-283.

GUO Yan-Xun-；Ma-Shi-Yin. Antitumor effects of metformin[J]. Journal of International Oncology, 2015, 42(4): 281-283.

参考文献

［1］ Lalau JD. Lactic acidosis induced by metformin: incidence, management and prevention［J］. Drug Saf, 2010, 33(9): 727740. ［2］ Zhang ZJ, Bi Y, Li S, et al. Reduced risk of lung cancer with metformin therapy in diabetic patients: a systematic review and metaanalysis［J］. Am J Epidemiol, 2014, 180(1): 1114. ［3］ Chen WW, Shao YY, Shau WY, et al. The impact of diabetes mellitus on prognosis of early breast cancer in Asia［J］. Oncologist, 2012, 17(4): 485491. ［4］ Pollak MN. Investigating metformin for cancer prevention and treatment: the end of the beginning［J］. Cancer Discov, 2012, 2(9): 778790. ［5］ Alimova IN, Liu B, Fan Z, et al. Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro［J］. Cell Cycle, 2009, 8(6): 909915. ［6］ Deng XS, Wang S, Deng A, et al. Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triplenegative breast cancers［J］. Cell Cycle, 2012, 11(2): 367376. ［7］ Menendez JA, OliverasFerraros C, Cufi S, et al. Metformin is synthetically lethal with glucose withdrawal in cancer cells［J］. Cell Cycle, 2012, 11(15): 27822792. ［8］ Liu PP, Liao J, Tang ZJ, et al. Metabolic regulation of cancer cell side population by glucose through activation of the Akt pathway［J］. Cell Death Differ, 2014, 21(1): 124135. ［9］ Singh S, Singh PP, Singh AG, et al. Antidiabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and metaanalysis［J］. Am J Gastroenterol, 2013, 108(4): 510519. ［10］ Bao B, Wang Z, Ali S, et al. Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells［J］. Cancer Prev Res (Phila), 2012, 5(3): 355364. ［11］ Lonardo E, Cioffi M, Sancho P, et al. Metformin targets the metabolic achilles heel of human pancreatic cancer stem cells［J］. PLoS One, 2013, 8(10): e76518. ［12］ Gou S, Cui P, Li X, et al. Low concentrations of metformin selectively inhibit CD133+ cell proliferation in pancreatic cancer and have anticancer action［J］. PLoS One, 2013, 8(5): e63969. ［13］ Zhang T, Guo P, Zhang Y, et al. The antidiabetic drug metformin inhibits the proliferation of bladder cancer cells in vitro and in vivo［J］. Int J Mol Sci, 2013, 14(12): 2460324618. ［14］ Zhang ZJ, Zheng ZJ, Kan H, et al. Reduced risk of colorectal cancer with metformin therapy in patient with type 2 diabetes: a metaanalysis［J］. Diabetes Care, 2011, 34(10): 23232328. ［15］ Hosono K, Endo H, Takahashi H, et al. Metformin suppresses colorectal aberrant crypt foci in a shortterm clinical trial［J］. Cancer Prev Res(Phila), 2010, 3(9): 10771083. ［16］ Coco C, Zannoni GF, Caredda E, et al. Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients［J］. J Exp Clin Cancer Res, 2012, 31(1): 7181. ［17］ Feng YH, Wu CL, Shiau AL, et al. MicroRNA21mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5fluorouracil and metformin in colon cancer cells［J］. Int J Mol Med, 2012, 29(5): 920926. ［18］ Saito T, Chiba T, Yuki K, et al. Metformin, a diabetes drug, eliminates tumorinitiating hepatocellular carcinoma cells［J］. PLoS One, 2013, 8(7): e70010. ［19］ Chen H, Liu X, Chen H, et al. Role of SIRT1 and AMPK in mesenchymal stem cells differentiation［J］. Ageing Res Rev, 2014, 13: 5564. ［20］ Hadad S, Iwamoto T, Jordan L, et al. Evidence for biological effects of metformin in operable breast cancer: a preoperative, windowofopportunity, randomized trial［J］. Breast Cancer Res Treat, 2011, 128(3): 783794. ［21］ Lliopoulos D, Hirsch HA, Struhl K. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types［J］. Cancer Res, 2011, 71(9): 31963201. ［22］ Lliopoulos D, Hirsch HA, Struhl K. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types［J］. Cancer Res, 2011, 71(9): 31963201. ［23］张艳飞, 薛耀明, 江颖娟，等. 二甲双胍联合5氟尿嘧啶抑制人结肠癌细胞SW620生长的实验研究［J］. 实用医学杂志, 2013, 29(17): 27842786. ［24］ Xu W, Lin H, Zhang Y, et al. Compound Kushen injection suppresses human breast cancer stemlike cells by downregulating the canonical Wnt/betacatenin pathway［J］. J Exp Clin Cancer Res, 2011, 30(1): 103108. ［25］ Takatani T, Minagawa M, Takatani R, et al. AMP activated protein kinase attenuates Wnt/βcatenin signaling in human osteoblastic Saos2 cells［J］. Mol Cell Endocrinol, 2011, 339(12): 114119. ［26］ Zhang T, Wang X, He D. Metformin sensitizes human bladder cancer cells to TRAILinduced apoptosis through mTOR/S6K1mediated downregulation of cFLIP［J］. Anticancer Drugs, 2014, 25(8): 887897. ［27］ Zannella VE, Dal PA, Muaddi H, et al. Reprogramming metabolism with metformin improves tumor oxygenation and radiotherapy response［J］. Clin Cancer Res, 2013, 19(24): 67416750. ［28］ Li H, Chen X, Yu Y, et al. Metformin inhibits the growth of nasopharyngeal carcinoma cells and sensitizes the cells to radiation via inhibition of the DNA damage repair pathway［J］. Oncol Rep, 2014, 32(6): 25962604. ［29］ Storozhuk Y, Hopmans SN, Sanli T, et al. Metformin inhibits growth and enhances radiation response of nonsmall cell lung cancer (NSCLC) through ATM and AMPK［J］. Br J Cancer, 2013, 108(10): 20212032. ［30］ Bayraktar S, HernadezAya LF, Lei X, et al. Effect of metformin on survival outcomes in diabetic patients with triple receptornegative breast cancer［J］. Cancer, 2012, 118(5): 12021211.

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲. 血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊. 局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	袁健, 黄燕华. Hp-IgG抗体联合血清DKK1、sB7-H3对早期胃癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(6): 338-343.
[4]	陈红健, 张素青. 血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[5]	郭泽浩, 张俊旺. PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[6]	张百红, 岳红云. 新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[7]	许凤琳, 吴刚. EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[8]	王盈, 刘楠, 郭兵. 抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[9]	张蕊, 褚衍六. 基于FIT与肠道菌群的结直肠癌风险评估模型的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 370-375.
[10]	高凡, 王萍, 杜超, 褚衍六. 肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[11]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东. ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[12]	刘静, 刘芹, 黄梅. 基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[13]	杨琳, 路宁, 温华, 张明鑫, 朱琳. 炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.
[14]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝. 癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.
[15]	张宁宁, 杨哲, 檀丽梅, 李振宁, 王迪, 魏永志. 宫颈细胞DNA倍体分析联合B7-H4和PKCδ对宫颈癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(5): 286-291.