Oxaliplatin (Oxa) is used as first-line chemotherapy in colorectal cancer (CRC), one of the most incidental and mortal types of cancer in worldwide. Acquired resistance to Oxa is an inevitable problem and the major reason for the failure of CRC therapy. Vitamin C, as a glycolysis inhibitor, selectively uptakes by KRAS and BRAF mutant CRC cells and induces cytotoxic effects by impairing cellular energy metabolism. We aimed to evaluate the cytotoxic activity of vitamin C on Oxa-resistant HCT116 colorectal cancer cells. Oxa-resistant HCT116 colorectal cancer cells were established by the exposure of HCT116 cells to increasing concentrations (0.5-4.3 µM) of Oxa. The cells which had grown exponentially in the presence of 4.3 μM Oxa were considered as Oxa-resistant HCT116 cells (HCT116/Oxa4.3). The viability of HCT116 and HCT116/Oxa4.3 cells at 48 h after a 2 h-treatment with vitamin C was assessed using MTT assay. The IC50 values of vitamin C against HCT116 and HCT116/Oxa4.3 cells were 0.6 ± 0.02 mM and 0.28 ± 0.08 mM, respectively, indicating that Oxa-resistant HCT116 cells were more sensitive to vitamin C compared to the parental cells. The results of colony formation indicated that vitamin C reduced the clonogenicity of both cells in a concentration-dependent manner with higher inhibitory potential against HCT116/Oxa4.3 cells. Wound healing assay results showed that the migration ability of HCT116/Oxa4.3 cells was lower than that of HCT116 cells and vitamin C had more anti-migratory activity against HCT116/Oxa4.3 cells compared to the control cells. In conclusion, HCT116/Oxa4.3 cells exhibited more sensitive than the parental cells to vitamin C, suggesting that vitamin C might be a promising candidate for further investigation for the treatment of oxaliplathin-resistant colorectal cancer cells.

Keywords