Nedaplatin sensitization of cisplatin-resistant human non-small cell lung cancer cells

摘要

Cisplatin (DDP) has been one of the most widely used chemotherapy drugs for advanced non-small cell lung cancer. However, the increase in the number of DDP-resistant cancer cells has become a major impediment in the clinical management of cancer. In the present study, for the first time, the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay was used to demonstrate that nedaplatin (NDP) could have a stronger inhibitory effect than DDP alone in DDP-resistant A549 (A549DDP) cells and that it could attenuate the resistance of these cells. Additionally, flow cytometry analysis showed that the apoptosis rate of these resistant cells when exposed to NDP was markedly increased and the number of cells in the G2 stage of the cell cycle was significantly increased. Furthermore, western blot analysis indicated that NDP decreased the protein expression of P-glycoprotein, tumor protein p53 and B-cell lymphoma 2, and increased the expression of Bcl-2-associated X protein, all of which could possibly improve the NDP intracellular drug concentration and promote cell apoptosis. These observations suggested that NDP could have higher efficacy in DDP-resistant lung cancer cells, and further studies applying more detailed analyses are warranted to elucidate the mechanism(s) behind this effect.