Effect of palliative radiotherapy and cyclin-dependent kinase 4/6 inhibitor on breast cancer cell lines.

Abstract

The most prevalent disease in the world and the main reason for women mortality from cancer is breast cancer. The recommended treatment for hormone receptor-positive metastatic breast cancer (MBC) is cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), Abemaciclib. Radiotherapy (RT) is one of the main options to control breast cancer. This work intended to examine the impact of CDK 4/6i and palliative radiation on human breast cancer cell lines. Breast cancer cell lines (MCF7, MDA-MD-468, and MDA-MD-231) were treated with varying doses of Abemaciclib and left to incubate for 48 h. Different radiation doses were applied to the lines that had the best IC50. The intrinsic treatment objectives for MBC are presented in this study, along with the PI3K/AKT/mTOR pathway; CDK4, CDK6, and the NF-κβ/TGF-β pathway; BAX/BcL2, P53; caspase-3, caspase-6, caspase-7, caspase-8, and caspase-9; cytokeratin 18 (CK18); cycloxygenase-2 (COX2); IL-6; IL1β; matrix metalloproteinases (MMP2 and MMP9); and oxidative stress markers. The biochemical assays revealed that abemaciclib hindered the progression of breast cancer cells MDA-MB-231 and MCF-7 and enhanced RT (10 Gy) by provoking cell cycle arrest throughout the restraint of CDK4 and CDK6 expression and increasing apoptosis, in addition to decreasing the PI3K/AKT/mTOR and NF-κβ/TGF-β pathway expression; inhibiting CK18 and COX2 activity; boosting the protein concentration of BAX and P53; and decreasing Bcl-2, IL-6, IL-1β, MMP2, and MMP9, modulating oxidative stress markers. These results implied potential effects of radiation and CDK4/6i abemaciclib on breast cancer cell lines.