BI2536 – A PLK inhibitor augments paclitaxel efficacy in suppressing tamoxifen induced senescence and resistance in breast cancer cells

摘要: Tamoxifen resistance is a multifaceted phenomenon, characterized by the constitutive activation of multiple signaling cascades that provide an additional survival advantage to cells. Ground studies related reverse tamoxifen employing chemotherapeutic drugs specifically inhibit proteins, those aberrantly expressed, are required. Seminal showed p38 and VEGF play crucial role in acquiring tamoxifen. In this view, we had chosen paclitaxel, mitotic inhibitor with anti-proliferative effects against wide array cancers study. Further mitigate undesirable complications paclitaxel (PAC), employed drug combination along BI2536 (BI), PLK for study sensitize resistant cells apoptosis. MCF 7/TAM T-47D/TAM were treated PAC, BI (BI-PAC) evaluated its anticancer activity through apoptotic western blot analysis. Modulatory BI-PAC on inactivation affirmed immunofluorescence potential studies. Results reveal subjected apoptosis drug(s) treatment which was confirmed cytotoxicity, annexin Further, nuclear morphological TUNEL assays. Immunoblot results revealed upregulation proapoptotic Bax, cleaved caspase 9 Bcl-2, MDM2, Cox-2, P-Gly down regulation after 24h treatments. Moreover, phospho further construed rationale behind deduced NF-κB inducing The efficacy combinations inactivating treatments inhibition mediated senescence Overall, our observations new therapeutic sensitizes targeting downstream molecules subsequently reduces extracellular levels.