Oxaliplatin is a third-generation platinum analog that can interfere with DNA replication and transcription by DNA damage. Continuous exposure of oxaliplatin resulted in resistance to oxaliplatin but no mechanisms of oxaliplatin-resistance were reported. In this study, oxaliplatin resistant cells were established using HCT116, HT29, SW480 and SW620 colon cancer cells by gradually increasing drug concentration up to a maximum of 2 µM at least for 3 month. The 50% inhibitory concentrations of cell growth (IC50) of oxaliplatin were 5.34, 9.88, 10.1 and 9.49-fold higher in oxaliplatin resistant HCT116, HT29, SW480, and SW620 cells, respectively, compared to their respective parental cells. One mechanism is that the expression of AKT and mTOR proteins were overexpressed in the oxaliplatin-resistant colon cancer cells. In addition, the expression of LC3B, an autophagy marker, decreased along with increasing AKT/mTOR signals, which caused the increase in glucose metabolism to produce energy for cell survival in oxaliplatin-resistant cancer cells. Taken together, oxaliplatin-resistance might be mediated through the activation of AKT/mTOR pathway in colon cancer cells, and AKT/mTOR might be a potential targets for oxaliplatin-resistance in human colon cancers.
