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Introduction: There is growing evidence about the use of antioxidants to reduce the side effects of chemotherapy and cancer drug resistance. Therefore, this study aimed to use vitamin C as an antioxidant and determine its effect on drug resistance in HT29 cells.
 
Materials & Methods: During this case-control study, HT29 cells were first cultured and evaluated by MTT assay for cell death in the presence of vitamin C and 5FU. DAPI staining was also performed to visualize cell apoptosis. After RNA extraction and cDNA preparation, to determine the molecular mechanism of apoptosis by the drug and the inhibition effect or aggravation of vitamin C on cellular signaling of apoptosis, expression of growth-related genes and apoptosis of Caspase-3 and Bax were measured by real-time PCR.
 
Findings: The results of the MTT test showed that vitamin C had no significant effect on cell apoptosis induced by 5-FU. DAPI and DNA ladder assay results from HT29 cells showed qualitative changes in cell apoptosis. In addition, real-time PCR results revealed increased expression of Bax and Caspase-3 in HT29 colon cancer cells treated with chemotherapy.
 
Discussions & Conclusions: Our findings showed that vitamin C did not prevent the effect of chemo drug although it had no positive effect on the growth of cancer cells. Therefore, vitamin C intake by patients undergoing chemotherapy will not affect the drug's effect on the tumor and may protect the patient from side effects.