Effects of Diclofenac on 5-Fluorouracil Cytotoxicity in Colorectal Cancer (Caco-2) Cells

Abstract

Alongside surgery and chemotherapy in the treatment of colorectal cancer, combination therapy strategies are cited as a potential way to improve treatment outcomes. It has been delineated that nonsteroidal anti-inflammatory drugs (NSAİDs) act as tumor suppressors in various cancer cells, induce apoptosis and increase the cytotoxic activity of some antineoplastic drugs. In the study, we aimed to determine the effects of diclofenac on cell viability in human colorectal cancer (caco-2) cell line, alone and in combination with 5-fluorouracil (5-FU), the backbone of chemotherapy. For this purpose, the effects of separate and combined applications of two drugs on the cell viability were investigated for 24 hours by dose-dependent MTT assay. Then, the effects of combinations of 5-FU (at IC50 and IC50/2 concentration) and wide concentrations of diclofenac (15.6-1000 μM) on the cell viability were evaluated for 24 hours. The IC50 values of diclofenac and 5-FU were found to be 324.7 μM and 18.56 mM, respectively. The viability of cells treated with 5-FU (20 and 10 mM) decreased significantly with diclofenac doses of 250 μM and above, dose-dependently (p<0.05). In conclusion, diclofenac alone was also cytotoxic in caco-2 cells, and in combination with 5-FU, it can cause a decrease in cell viability with a synergistic effect. Our findings may provide the data for combination or alternative approaches, especially against colorectal cancer. Efficacy in chemotherapy should be evaluated with in vivo and clinical studies.