HSP90靶向抑制剂P7与多西紫杉醇联用对三阴性乳腺癌细胞的协同抗肿瘤作用

摘要

目的 探讨双功能小分子多肽LPLTPLP(P7)和化疗药物多西紫杉醇(DTX)联用对三阴性乳腺癌细胞系MDA-MB-231的影响.方法 多肽P7与DTX两药联合处理三阴性乳腺癌细胞系MDA-MB-23148 h后,用SRB法检测细胞存活;用等效图解法分析其作用;用流式细胞计量术检测多肽P7、化疗药DTX及两药联用后MDA-MB-231细胞凋亡率;用蛋白免疫印迹技术检测多肽P7、化疗药DTX及两药联用后MDA-MB-231细胞凋亡相关蛋白的表达.结果 P7与 DTX 对细胞存活具有协同作用;联合用药组细胞凋亡率为60.6%,是 DTX 单药组凋亡率(34.5%)的1.8倍;P7与DTX联合用药干预48 h后,凋亡相关蛋白Bcl-2与Bax表达量的比值显著下调.结论 P7协同化疗药物DTX能显著提高细胞的凋亡率,其机制可能与两药联合后调控促凋亡蛋白Bax和凋亡蛋白Bcl-2表达相关.%Objective To evaluate the effect of docetaxel(DTX)combined with a heptapeptide(LPLTPLP, namely P7)on the human triple-negative breast cancer cell line MDA-MB-231 in vitro.Methods The cell viability was measured by SRB assay followed by evaluation of their combination effect using the isobologram.Flow cytometry was performed to quantify apoptotic cells following treatment of DTX,P7 and DTX combined with P7 and the ex-pressions of the apoptosis-related proteins were determined by Western blot analysis.Results P7 synergized with DTX in cell viability detection.The apoptotic rate was highly increased with increasing Bax /Bcl-2 ratio after MDA-MB-231 cells were exposed to DTX and P 7 combination.Conclusions Combination of P 7 and DTX has synergistic effects on MDA-MB-231 cells characterized by increasing apoptosis activation,in which the expression of pro-apop-totic protein Bax increased with a decline in apoptotic protein Bcl-2.