Concomitant effects of paclitaxel and celecoxib on genes involved in apoptosis of triple-negative metastatic breast cancer cells

Abstract

Although triple-negative breast cancer accounts for less than one-fifth of breast cancers, it has a higher rate of metastasis and mortality. This study investigated the effects of combination treatment with paclitaxel and celecoxib on the expression of genes involved in the apoptosis of triple-negative metastatic breast cancer cells. MDA-MB-231 cells were cultured and then treated with certain concentrations of celecoxib (CLX), paclitaxel (PTX), and combination of them for 24 and 48 h. Cell viability was assessed by the MTT method. The real-time PCR method was utilized to assess the expression level of the genes involved in apoptosis. Western blotting was used for evaluating protein expression. IC₅₀ values for CLX and PTX were 73.95 μM and 3.15 μM, respectively. The results demonstrated that PTX, CLX, and PTX + CLX significantly (p < 0.05) reduced cell viability. The comparison of combination treatment with PTX showed a significant increase in caspase 3 gene expression at both time points, in Bax gene expression after 48 h, and a remarkable decrease in Bcl-2 gene expression at both times. Western blotting results were in line with genes' expression. These findings indicate that a combination of PTX and CLX results in a significantly more reduction in cell viability of breast cancer cells. In addition, it seems CLX may be an effective agent in regulating the expression level of caspase 3, Bax, and Bcl-2 when combined with PTX.

Keywords: Apoptosis; Celecoxib; Cox-2; MDA-MB-231; Paclitaxel; Triple-negative breast cancer.