人胃癌细胞系MKN-45中二甲双胍对顺铂的拮抗作用

王晓东,李红涛,杨涛,姚旻,朱予津

武警医学 ›› 2015, Vol. 26 ›› Issue (10) : 1015-1020.

PDF(2422 KB)
PDF(2422 KB)
武警医学 ›› 2015, Vol. 26 ›› Issue (10) : 1015-1020.
论 著

人胃癌细胞系MKN-45中二甲双胍对顺铂的拮抗作用

  • 王晓东1,李红涛2,杨涛2,姚旻2,朱予津2
作者信息 +

Preliminary study on the antagonistic effect of metformin on cisplatinin human gastric cancer MKN-45 cellline

  • WANG Xiaodong1, LI Hongtao2, YANG Tao2, YAO Min2, and ZHU Yujin2
Author information +
文章历史 +

摘要

目的 初步研究二甲双胍(metformin,Met)和Met联合顺铂(cisplatin, Cisp)对人胃癌MKN-45细胞系的抗癌作用。方法 应用不同浓度Met和Cisp单独或联合处理人胃癌MKN-45细胞系,MTT法分析细胞存活率,RT-PCR检测生存素、mTOR和Akt的mRNA表达水平,流式细胞仪检测细胞凋亡。结果 单独使用Met可抑制增殖并诱导凋亡;Met联合Cisp时,可降低Cisp的抗增殖作用,且生存素、Akt和mTOR的mRNA表达明显增加(P<0.05)。Met对Cisp的拮抗作用可能是通过生存素、Akt和mTOR信号通路调节。结论 Met能抑制人胃癌MKN-45细胞系对Cisp化疗的敏感性,在患有2型糖尿病的胃癌患者中,应该慎重将Met与Cisp联合使用。

Abstract

Objective To evaluate the effect of Metformin and Metformin combined with Cisplatin on human gastric MKN-45 cell line. Methods Treated the human gastric cancer MKN-45 cell line withof the Metformin alone or Metformin combined withCisplatinby different concentrations,thenanalysed the cell survival rate by MTT,checked mRNA levels of survivin, mTOR, and Akt by real-time PCR, and assessed the Cell apoptosis by flow cytometry. Results Metformin alone could inhibit theproliferation and induce apoptosis, but it diminish anti-proliferative effects of theCisplatin when they were used in combination. When MKN-45 cells were treated with Metformin and Cisplatin, the expression of survivin and mTOR were increased. The antagonistic effect of the Metformin on the Cisplatinmight be through survivin, Akt and mTOR signaling pathways. Conclusions Met can inhibit the chemotherapy sensitivity of CispinMKN-45 human gastric cancer cell line.For gastric cancer patients with Type 2 Diabeteswho treated with Cisp,Met should be carefully used.

关键词

二甲双胍 / 顺铂 / 胃癌 / 生存素

Key words

metformin / cisplatin / gastric cancer / survivin

引用本文

导出引用
王晓东,李红涛,杨涛,姚旻,朱予津. 人胃癌细胞系MKN-45中二甲双胍对顺铂的拮抗作用[J]. 武警医学. 2015, 26(10): 1015-1020
WANG Xiaodong, LI Hongtao, YANG Tao, YAO Min, and ZHU Yujin. Preliminary study on the antagonistic effect of metformin on cisplatinin human gastric cancer MKN-45 cellline[J]. Medical Journal of the Chinese People Armed Police Forces. 2015, 26(10): 1015-1020
中图分类号: R753.2   

参考文献

[1] Iliana C Lega, Prakesh SShah, David Margel, et al. The effect of metformin on mortality following cancer among patients with diabetes[J].Cancer Epidemiol Biomarkers Prev, 2014, 23(10): 1974-1984.
[2] Cao J, Meng S, Chang E, et al. Low concentrations of metformin suppress glucose production in hepatocytes through AMP-activated protein kinase (AMPK)[J]. J Biol Chem,2014, 289(30):20435-20446.
[3] Lee M S, Hsu C C, Wahlqvist M L, et al. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals[J].BMC Cancer, 2011, 11: 20.
[4] Zhang H, Gao C, Fang L, et al.Metformin and reduced risk of hepatocellular carcinoma in diabetic patients: a meta-analysis[J]. Scand J Gastroenterol, 2013,48(1):78-87.
[5] Vallianou N G, Evangelopoulos A, Kazazis C.Metformin and cancer[J].Rev Diabet Stud, 2013,10(4):228-235.
[6] Jiang X, Ma N, Wang D,et al.Metformin inhibits tumor growth by regulating multiple miRNAs in human cholangiocarcinoma[J].Oncotarget,2015,6(5):3178-3194.
[7] Oppong B A, Pharmer L A, Oskar S, et al.The effect of metformin on breast cancer outcomesin patients with type 2diabetes[J].Cancer Med,2014, 3(4):1025-1034.
[8] Qu C, Zhang W, Zheng G, et al. Metformin reverses multidrug resistance and epithelial-mesenchymal transition (EMT) via activating AMP-activated protein kinase (AMPK) in human breast cancer cells[J].Mol Cell Biochem, 2014, 386(1-2):63-71.
[9] Hadad S M, Hardie D G, Appleyard V,et al.Effects of metformin on breast cancer cell proliferation, the AMPK pathway and the cell cycle[J].Clin Transl Oncol, 2014, 16(8):746-752.
[10] Andreas R de Biasi, Jonathan Villena-Vargas, Prasad S. Adusumilli. Cisplatin-Induced antitumor immunomodulation: A review of preclinical and clinical evidence[J]. Clin Cancer Res, 2014, 20(11): 5384-5391.
[11] Chan J,Jung H H,Yang J Y,et al.Protectiveeffect of metformin against cisplatin- induced ototoxicity in an auditory cell line[J].J Assoc Res Otolaryngol, 2014, 15(2):149-158.
[12] Quattrini I, Conti A, Pazzaglia L, et al. Metformin inhibits growth and sensitizes osteosarcoma cell lines to cisplatin through cell cycle modulation[J].Oncol Rep, 2014, 31(1):370-375.
[13] Uehara T, Mitsuhashi A, Tsuruoka N, et al.Metformin potentiates the anticancer effects of cisplatin under normoxic conditions in vitro[J].Oncol Rep, 2015, 33(2):744-750.
[14] Huang J, Lyu H, Wang J, et al. MicroRNA regulation and therapeutic targeting of survivin in cancer[J].Am J Cancer Res, 2014, 5(1):20-31.
[15] Fock K M.Review article: the epidemiology and prevention of gastric cancer[J]. Aliment Pharmacol Ther, 2014, 40(3):250-260.
[16] Ryan J O, SarojNiraula, VukStambolic, et al. Metformin in cancer: translational challenges[J]. J Mol Endocrinol, 2012, 48(3): 31-43.
[17] Zhuang Y, Chan D K, Haugrud A B, et al. Mechanisms by which low glucose enhances the cytotoxicity of metformin to cancer cells both in vitro and in vivo[J]. PLoS One, 2014, 9(9):e108444.
[18] Dallaglio K, Bruno A, Cantelmo A R, et al.Paradoxic effects of metformin on endothelial cells and angiogenesis[J].Carcinogenesis, 2014,35(5):1055-1066.
[19] Rattan R, Graham R P, Maguire J L, et al.Metformin suppresses ovarian cancer growth and metastasis with enhancement of cisplatincytotoxicity in vivo[J].Neoplasia, 2011, 13(5):483-491.
[20] Xie Y, Peng Z, Shi M, et al.Metformin combined with p38 MAPK inhibitor improves cisplatin sensitivity in cisplatinresistantovarian cancer[J].Mol Med Rep, 2014, 10(5):2346-2350.
[21] Hongyu LIU, Christian Scholz, Chuanbing ZANG, et al. Metformin and the mTOR inhibitor everolimus (RAD001) sensitize breast cancer cells to the cytotoxic effect of chemotherapeutic drugs in vitro[J]. Anticancer Res, 2012, 32(5): 1627-1637.
[22] Zi F M, He J S, Li Y,et al.Metformin displays anti-myeloma activity and synergistic effect with dexamethasone in in vitro and in vivo xenograftmodels[J].Cancer Lett, 2015, 356(2):443-453.
[23] Janjetovic K, Harhaji-Trajkovic L, Misirkic-Marjanovic M, et al.In vitro and in vivo anti-melanoma action of metformin[J].Eur J Pharmacol, 2011, 668(3):373-382.
[24] Han G, Gong H, Wang Y,et al.AMPK/mTOR-mediated inhibition of survivin partly contributes to metformin-induced apoptosis in human gastric cancer cell[J].Cancer Biol Ther, 2015,16(1):77-87.
[25] Lesan V, Ghaffari S H, Salaramoli J, et al.Evaluation of antagonistic effects of metformin with Cisplatin in gastric cancer cells[J].Int J HematolOncol Stem Cell Res, 2014, 8(3):12-19.
[26] Cao W, Yang W, Fan R, et al.miR-34a regulates cisplatin-induce gastric cancer cell death by modulating PI3K/AKT/survivinpathway[J].Tumour Biol, 2014 ,35(2):1287-1295.
[27] Ettl T, Viale-Bouroncle S, Hautmann M G, et al.AKT and MET signalling mediates antiapoptoticradioresistance in head neck cancer cell lines[J].Oral Oncol,2015,51(2):158-63.
[28] Tsubaki M, Takeda T, Ogawa N, et al.Overexpression of survivin via activation of ERK1/2, Akt, and NF-κB plays a central role in vincristine resistance in multiple myeloma cells[J].Leuk Res, 2015, 39(4):445-452.
[29] Hsin I L, Ou C C, Wu M F, et al.GMI, an Immunomodulatory Protein from Ganodermamicrosporum, Potentiates Cisplatin-Induced Apoptosis via Autophagy in Lung Cancer Cells[J].Mol Pharm, 2015, 12(5):1534-1543.

PDF(2422 KB)

Accesses

Citation

Detail

段落导航
相关文章

/