Genistein enhances the effect of cisplatin on the inhibition of non-small cell lung cancer A549 cell growth in vitro and in vivo

Although cisplatin (DDP) has been reported to be a promising antitumor therapy for non-small cell lung cancer (NSCLC), the effectiveness of the treatment remains limited due to an inherent tumor resistance to DDP. Genistein (GEN) is an abundant, naturally occurring isoflavonoid found in soy products that has been demonstrated to increase the anti-neoplastic activity of certain chemotherapy drugs in multiple tumor types. In the present study, DDP in combination with GEN was selected as a potential treatment to suppress tumor growth and simultaneously reduce the doses of the two drugs required for the treatment of NSCLC. Cell growth inhibition, apoptosis, cell cycle distribution and receptor signaling assays were conducted. In the in vivo study, DDP and GEN, either alone or in combination, were used to treat a xenograft model of the A549 cells. It was found that the combination of low concentrations of DDP and GEN induced significantly greater growth inhibition (P<0.01) and increased apoptosis in the A549 cells compared with either agent alone. In addition, DDP in combination with GEN could significantly suppress tumor growth in vivo compared with either agent alone. Combination treatment significantly suppresses constitutive phosphorylation of AKT and phosphoinositide-3 kinase, which may contribute to the inhibition of tumor growth. Overall, the present data suggested that GEN can increase the anti-neoplastic activity of DDP and that a combination of GEN and DDP is a potential drug candidate for the treatment of NSCLC.