人胃癌细胞系MKN-45中二甲双胍对顺铂的拮抗作用

Abstract
Figure/Table
References
Related Citation (15)

Download: PDF (2422 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

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.

Key words： metformin cisplatin gastric cancer survivin

Received: 26 January 2015

ZTFLH:

R753.2

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	WANG Xiaodong
	LI Hongtao
	YANG Tao
	YAO Min
	and ZHU Yujin

Cite this article:

WANG Xiaodong,LI Hongtao,YANG Tao等. Preliminary study on the antagonistic effect of metformin on cisplatinin human gastric cancer MKN-45 cellline[J]. Med. J. Chin. Peop. Armed Poli. Forc., 2015, 26(10): 1015-1020.

URL:

http://journal08.magtechjournal.com/Jwk_wjyx/EN/ OR http://journal08.magtechjournal.com/Jwk_wjyx/EN/Y2015/V26/I10/1015

[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[15]	Fock K M.Review article: the epidemiology and prevention of gastric cancer[J]. Aliment Pharmacol Ther, 2014, 40(3):250-260.
[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.
[16]	Ryan J O, SarojNiraula, VukStambolic, et al. Metformin in cancer: translational challenges[J]. J Mol Endocrinol, 2012, 48(3): 31-43.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.