Investigation of the influence of vitamin C against oxaliplatin-resistant HCT۱۱۶ colorectal cancer cells

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 HCT۱۱۶ colorectal cancer cells. Oxa-resistant HCT۱۱۶ colorectal cancer cells were established by the exposure of HCT۱۱۶ cells to increasing concentrations (۰.۵-۴.۳ μM) of Oxa. The cells which had grown exponentially in the presence of ۴.۳ μM Oxa were considered as Oxa-resistant HCT۱۱۶ cells (HCT۱۱۶/Oxa۴.۳). The viability of HCT۱۱۶ and HCT۱۱۶/Oxa۴.۳ cells at ۴۸ h after a ۲ h-treatment with vitamin C was assessed using MTT assay. The IC۵۰ values of vitamin C against HCT۱۱۶ and HCT۱۱۶/Oxa۴.۳ cells were ۰.۶ ± ۰.۰۲ mM and ۰.۲۸ ± ۰.۰۸ mM, respectively, indicating that Oxa-resistant HCT۱۱۶ 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 HCT۱۱۶/Oxa۴.۳ cells. Wound healing assay results showed that the migration ability of HCT۱۱۶/Oxa۴.۳ cells was lower than that of HCT۱۱۶ cells and vitamin C had more anti-migratory activity against HCT۱۱۶/Oxa۴.۳ cells compared to the control cells. In conclusion, HCT۱۱۶/Oxa۴.۳ 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.

کلیدواژه ها:

Colon cancer ، Oxaliplathin ، Drug resistant ، Vitamin C