Effects of metformin and cisplatin on human lung cancer xenograft in nude mice

Abstract

Objective This study is designed to evaluate the effects of metformin combined with cisplatin on tumor growth,expressions of Survivin,matrix metalloproteinase-2(MMP-2),and Ki67 in lung cancer xenograft on nude mice,to potentially develop new effective drugs for the treatment of lung caner. Methods Human lung cancer xenograft study model was established. The nude mice were randomly divided into metformin-treated group, cisplatin-treated group, metformin combined with cisplatin-treated group and control group.Forty-two days after administration,all the nude mice were sacrificed and tumor tissues were sampled.The expressions of Survivin,MMP-2,and Ki67 proteins in the tumor tissues were detected by immumohistochemical method.The expressions of Survivin,MMP-2,and Ki67 m RNA in the tumor tissue were detected by florescent real-time quantitative PCR. Results The tumor inhibition rate in metformin-treated group,cisplatin-treated group,and metformin combined with cisplatin-treated group was 28.97%,35.34%,and 54.65%,respectively.The expressions of Survivin, MMP-2,and Ki67 protein and m RNA in cisplatin-treated group and metformin combined with cisplatintreated group were lower than those in control group(all P< 0.05).Compared with control group,the expressions of MMP-2 protein and mRNA in metformin-treated group were reduced(all P< 0.05). Compared with metformin-treated group and cisplatin-treated group,the expressions of Survivin,MMP-2, and Ki67 protein and m RNA in metformin combined with cisplatin-treated group were reduced(all P< 0.05). Conclusions Metformin could inhibit MMP-2 expression.Cisplatin or metformin combined with cisplatin can inhibit the expressions of Survivin,MMP-2,and Ki67.Combination drug of metformin and cisplatin can enhance the anti-tumor efficacy. Key words: Lung caner; Metformin; Cisplatin; Survivin; Matrix metalloproteinase-2; Ki67