Armaghane Danesh Bimonthly Journal (Apr 2022)
Evaluation the Effects of Diclofenac and Oxaliplatin on the Expression of Caspase8 and Caspase9 Genes in Colorectal Cancer Cell Line(SW480)
Abstract
Background & aim: Apoptosis induction is one of the basic goals in the production of anticancer drugs. Evaluation of the relationship between non-steroidal anti-inflammatory drugs (NSAID) and apoptosis in cancer cells is promising. Therefore, the aim of the present study was to determine the combination of oxaliplatin and diclofenac drugs on the expression of caspase 8 and 9 genes in colorectal cancer cell line (SW480) using Real Time PCR. Methods: In the present experimental study conducted in 2019, SW480 colorectal cancer cells were treated with different concentrations of oxaliplatin and diclofenac, as well as a combination of diclofenac and oxaliplatin. The MTT method was used to check cell viability and the median inhibitory concentration (IC50) was obtained for each group, and the real-time PCR method was used to evaluate the expression of Caspase 8 and Caspase 9 genes. The collected data were analyzed using SPSS software and one-way variance statistical test and t-test. 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. 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.As a result, it is essential to investigate the possible use of diclofenac with oxaliplatin in the treatment of colon cancer.
