Investigation of the effect of Aurora B kinase inhibition on paclitaxel cytotoxicity

Cancer is the continuous proliferation of cells as a result of the loss of function of proteins that play a role in the growth, division, differentiation, development and programmed death of cells. Chemotherapeutic drugs used in the clinical treatment of cancer cause serious side effects and reduce quality of life. In addition, the desired therapeutic effect may not be achieved with chemotherapy. Personalized treatments are very important due to drug resistance to chemotherapeutic agents and serious side effects on patients. The combination of small molecule inhibitors and chemotherapeutic drugs can have a synergistic effect, reducing or eliminating side effects and being effective against acquired drug resistance. In this study, we investigated the effect of Aurora B kinase inhibition on paclitaxel cytotoxicity. BI 831266 molecule was used for Aurora B inhibition. The cytotoxic effects of mono- and combined treatment of BI 831266 and paclitaxel molecule were examined in MCF-7 human breast cancer cells. MCF-7 cells were treated with increasing doses of BI 831266 and paclitaxel molecule and their cytotoxic effects were determined by colony survival analysis. The combination treatment of BI 831266 and paclitaxel molecule was shown to inhibit the colony forming capacity of cancer cells by colony survival analysis. The expression levels of apoptotic signaling pathways and cell cycle proteins in MCF-7 cells treated with mono and combination treatments of BI 831266 and paclitaxel molecule were examined by Western blot method. The findings obtained in this study indicate that combination treatments of BI 831266 and paclitaxel molecule decreased cell viability, inhibited colony survival and caused apoptosis and DNA damage by upregulating the expression levels of apoptosis-related proteins. Keywords: BI 831266 molecule, Paclitaxel, Aurora kinases, Aurora Kinase B, MCF-7, Cell Cycle.