Effects And Mechanism Of PIB5PA Enhancing The Sensitivity Of Triple-negative Breast Cancer Cell Line MDA-MB-231 To Paclitaxel Treatment

Background and Objective Breast cancer is one of the most common malignancies in female,15 percent of which is called triple-negative breast cancer (TNBC) that does not express estrogen receptor, progesterone receptor and human epithelial growth factor receptor (EGF)-2. At present, the research progress on TNBC is relatively slow in worldwide. The chemotherapy is still the major treatment to postoperative patients. As anti-microtubules chemotherapy drug, Paclitaxel is the first choice to TNBC patients after operation. However, there are a large part of the TNBC patients who are resistance to Paclitaxel, in which the mechanism may be related to the activation of the PI3K/Akt signalling pathway. PIB5PA can inhibit the activation of PI3K/Akt signalling pathway. Whether the PIB5PA has the capacity to enhance the sensitivity of the TNBC to Paclitaxel treatment through this inhibitory pathway is still unknown, which is also the research focus of this subject Methods Breast cancer cell lines MCF-7 and MDA-MB-231 was cultured with different concentrations (0,0.l,0.2,0.3,0.4,0.5?mol-L-1)of Paclitaxel, Then MTT and flow cytometry propidium iodide (PI) staining assay was used to measure these two cell lines survival and apoptosis respectively. Also Western Blotting was applied to observe the Bcl-2 family expression at different time points after treated with 0.3?mol·-1 Paclitaxel. The cell line MDA-MB-231, which was less sensitive to Paclitaxel relatively, was transfected with pCGN-PIB5PA plasmids, followed by treatment of 0.3?mol·L-1 Paclitaxel for 24 hours. Then we detect the expression of PIB5PA, phosphorvlated AKt and Bcl-2 family using Western Blotting and evaluate the sensitivity of transfected cell line to Paclitaxel treatment by MTT and PI staining assay.Results After the treatment of Paclitaxel to Breast cancer cell lines MCF-7 and MDA-MB-231, the apoptosis of the cell lines MCF-7 was augmented significantly, while the cell lines MDA-MB-231 was less sensitive to Paclitaxel treatment. Relatively, Paclitaxel treatment promotes Bim expression in MCF-7 cell obviously, which is unaltered in MDA-MB-231 cell. After the overexpression of PIB5PA, the sensitivity of cell lineMDA-MB-231 to Paclitaxel treatment was significantly enhanced in comparison withthat transfected with control plasmids, showing the reduced cell survival and increased cell apoptosis. The mechanism may be related to up-regulation of Bim expression and decreasing Phosphorvlated AKt. Conclusion PIB5PA could enhance sensitivity obviously to Paclitaxel treatment, probably by promoting the Bim expression in triple-negative breast cancer cell line MDA-MB-231.