Determination of the cytotoxic and apoptotic effects of CDK 4/6 inhibitor abemaciclib on triple-negative breast cancer cells

INTRODUCTION AND OBJECTIVE: Triple negative breast cancer (TNBC) is a breast cancer subtype which lacks of gene expression estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER-2) and has poor prognosis and limited treatment options. In recent years, cyclin-dependent kinase (CDK) inhibitors that regulate cell cycle have attracted attention by researchers. However, there are limited studies on the effect of CDK inhibitors in the treatment of TNBC. Therefore, in this thesis, we aimed to determine the cytotoxic and apoptotic effects of abemaciclib, a CDK4/6 inhibitor, in TNBC cells. MATERIAL AND METHOD: Viability (WST-1), apoptosis (annexin V), cell cycle, AO/EB staining, gene expression (RT-PCR) and caspase-3 (ELISA) analyzes were performed in MDA-MB-231 TNBC cell line and MCF-10A control cells. RESULTS: Abemaciclib significantly reduced the viability of MDA-MB-231 and MCF-10A cell lines in a dose- and time-dependent manner (p<0.05). Additionally, abemaciclib induced apoptotic death and increased in the amount of cells in the G0/G1 phase. When expression levels of apoptosis-related (Bcl2 and Bax) genes and the cell cycle-related (Ccnd1 and Rb1) genes were investigated by RT-PCR method, abemaciclib caused down-regulation in the expression levels of Ccnd1 and Bcl-2 genes, and also significantly increased the expression level of the Bax gene in TNBC cells (p<0.05). Furthermore, we determined that the level of active caspase-3 through ELISA analysis significantly increased in MDA-MB-231 and MCF-10A cells depending on abemaciclib concentration (p<0.01). CONCLUSION: The potential therapeutic effect of abemaciclib on TNBC has been revealed in the current study. Our findings show that abemaciclib, which is used in the treatment of ER + HER2- breast cancer, also has cytotoxic and apoptotic effects in TNBC cells.