Evaluation the effects of diclofenac and oxaliplatin on the expression of caspase8 and caspase9 genes in Colorectal Cancer cell line(SW480)

Background and Aim: Induction of apoptosis is one of the main goals in the production of anticancer drugs. Recently, the evaluation of the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and apoptosis in cancer cells has been promising. Caspase8, caspase9. Methods: In this experimental-laboratory study, sw480 colorectal cancer cells were treated with different concentrations of oxaliplatin and diclofenac as well as a combination of diclofenac and oxaliplatin. MTT method was used to evaluate cell viability and median inhibition concentration (IC50) was obtained for each group. Real time PCR method was used to evaluate the expression of Caspase8 and caspase9 genes and finally to analyze the data. One-way analysis of variance and t-test were used Results: In oxaliplatin treatment with SW480 cells, concentrations of 25, 50, 100 and 200 μg / ml significantly reduced the viability of this category compared to the control (P <0.001). And median inhibition concentration of 65 μg / ml was calculated. In the treatment of cells with diclofenac, concentrations of 1000,500,250 μg / ml significantly reduced the viability of this category compared to controls (P <0.001), concentrations of 12.5, 25, 50, 100 and 200 μg / ml. Oxaliplatin in combination with 250 μg of diclofenac significantly reduced the viability of this class compared to the control (p <0.001) and the median inhibition concentration calculated with diclofenac equivalent to 32 μg / ml. Also, the combined treatment of diclofenac and Oxaliplatine led to a very significant increase in the expression of genes caspase8 and caspase9. (p <0.001) so that the expression of Caspase 8 gene increased about 3.7 times and Caspase9 expression increased about 1.8 times compared to the control in this experiment. Discussion and Conclusion: Diclofenac in combination with oxaliplatin can cause more cytotoxic effects compared to oxaliplatin alone in sw480 cancer cells. And if these two drugs are combined, a lower dose of oxaliplatin is needed to achieve this goal. The combination of diclofenac and oxaliplatin is associated with increased expression of caspase 8 and  caspase 9 genes, so it is important to investigate the possible use of diclofenac with oxaliplatin in the treatment of colon cancer.