Combination of metformin and oxaliplatin inhibits gastric cancer cell proliferation and induces apoptosis

Abstract

Background: Gastric cancer is one of the most common cancers worldwide. The disease has a poor prognosis, especially when the tumor becomes inoperable. The present study investigated the potential synergistic effects of oxaliplatin and metformin in gastric cancer cells. Methods: The effect of oxaliplatin and metformin on cell proliferation was assessed with CCK-8 assay in human gastric cancer cell lines SGC7901 and SNU-16, where, the IC50 and (combination index) CI values were determined. RT-PCR and Western blotting were used to determine mRNA and protein expression levels of cell cycleand apoptosis-related genes. The apoptotic rate was detected with flow cytometry in SGC7901 and SNU-16 cells. Results: The CCK-8 assay showed inhibited proliferation of SGC7901 and SNU-16 cells upon oxaliplatin or metformin treatment and an increase in inhibitory potency when the drugs were administered in combination. Similarly, cell apoptosis was increased in both cell lines in the combination group compared to the metformin and oxaliplatin groups. Both metformin and oxaliplatin reduced Bcl-2 and increased Bax and caspase-3 expression in SGC7901 and SNU-16; and these effects were enhanced when the drugs were used in combination. Conclusion: The combination of metformin and oxaliplatin inhibited proliferation and induced apoptosis in gastric cancer cells. The underlying mechanisms may be related to the suppression of cyclin D1, Bcl-2 and the increase of expression of Bax and caspase-3.