Background: Metformin, a drug widely used for type 2 diabetes, may also have anti-cancer properties. The purpose of this study was to examine the effect of metformin on cisplatin cytotoxicity in the gastric adenocarcinoma cells line (MKN45).

Materials and Methods: In this study, cells viability and apoptosis were measured using the (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay and flow cytometry, respectively. Moreover, the expressions of mammalian target of rapamycin, survivin and AKT genes were evaluated by RT-PCR. All experiments were performed in triplicate.

Results: The results showed that each of metformin and cisplatin separately reduced the viability of cancer cell, but in co-administration, metformin reduced the cytotoxicity of cisplatin. In co-administration, the survivin expression was increased followed by a reduction in cisplatin anti-cancer effect. Therefore, the antagonistic effect of drugs can be associated with survivin expression. The results also revealed that the anti-apoptotic effects of metformin co-administrated with cisplatin are associated with increased AKT expression.

Conclusion: It seems that in gastric cancers, metformin is not an appropriate choice to make cells sensitive to cisplatin and the antagonistic effects of the two drugs should be considered when they prescribed in combination.