CBX2 Enhances Paclitaxel Resistance via PI3K/AKT Signaling Pathway in Breast Cancer

Abstract Objective Paclitaxel resistance is a significant contributor to poor prognosis in breast cancer treatment. The expression of CBX2 is upregulated in breast cancer with paclitaxel resistance. But the role and mechanism of CBX2 in promoting drug resistance in breast cancer is still unclear. Methods The CBX2 gene expression was inhibited by gene knockdown technology. Cell activity was assessed through CCK8 assay. The apoptosis levels evaluated via flow cytometry. The gene expression levels were detected using Q-PCR. The protein expression level was detected with WB. Transcriptome sequencing was employed to identify differences in gene expression and pathways regulated by CBX2. Mitochondrial membrane potential was analyzed by JC-1 assay. Results With CBX2 gene knockdown, the p-gp protein expression level was decreased, cell activity was declined, apoptosis level was reduced, PI3K and AKT protein levels were decreased, Bcl-2 protein level was decreased, mitochondrial membrane potential loss, and the pro-apoptotic proteins BAX, Caspase9 and Caspase3 levels were increased. Conclusion CBX2 activates the PI3K-AKT signaling pathway, thereby enhancing the anti-apoptotic capacity of cells and promoting resistance to paclitaxel in breast cancer. Therefore, targeting CBX2 may represent a promising strategy for overcoming drug resistance in breast cancer therapy.