【摘要】 目的探讨β-榄香烯与紫杉醇对乳腺癌细胞株协同作用及其机制。方法体外分别以β-榄香烯注射液(2.5、5.0、10.0、20.0、40.0、80.0、160.0、320.0、640.0μg/mL)、紫杉醇注射液(0.00100、0.00200、0.00400、0.00800、0.01600、0.03125、0.06250、0.12500、0.25000μg/mL)作用24h和48h以及两药联合处理人乳腺癌细胞株MB-468细胞,SRB法检测增殖变化,流式细胞仪检测细胞凋亡和细胞周期分布,通过Westernblot检测干预后细胞周期蛋白依赖性激酶1(cyclin-dependent kinase,CDK1)、细胞周期蛋白B1(cyclin B1)、细胞周期调控蛋白P21cip1和P27kip1表达变化。结果单药β-榄香烯或紫杉醇对MB-468细胞株生长均有抑制作用,β-榄香烯24h和48h的IC50和IC20值分别为34.20、52.59和10.15、17.81μg/mL,紫杉醇24、48h的IC50值分别为2.449和1.698μg/mL。联合组(β-榄香烯和紫杉醇的浓度分别为20、40和0.016、0.008μg/mL)对乳腺癌MB-468细胞株的生长抑制率具有协同作用,Q值>1.15。β-榄香烯组(52.59μg/mL)cyclin-B1蛋白表达有明显的下降,联合组较紫杉醇单药组(1.698μg/mL)cyclin B1的表达水平也有降低,联合组P27kip1蛋白的表达较β-榄香烯和紫杉醇单药作用时有增加。结论β-榄香烯对紫杉醇具有协同作用,其可能机制是通过下调细胞周期蛋白cyclin B1表达和上调P27kip1表达有关。更多还原

【Abstract】 Objective To observe the synergistic effect of β-elemene Injection (βI) combined Paclitaxel Injection (PI) on breast cancer MB- 468 cells and to study possible mechanisms. Methods Breast cancer MB- 468 cells were treated with βI (2.5, 5.0, 10.0, 20.0, 40.0, 80.0, 160.0, 320.0, and 640.0 μg/mL), PI (0.00100, 0.00200, 0.00400, 0.00800, 0.01600, 0.03125, 0.06250, 0.12500, and 0.25000 μg/mL), and βI combined PI for 24 h and 48 h respectively. Cell proliferation was determined using SRB assay. Cell apoptosis and cell cycle phase distribution were detected using flow cytometry. The post-intervention expressions of cell cycle proteins [cyclin-dependent kinase (CDK1), cyclin-B1, P21cip1, and P27kip1] were detected by Western blot. Results β-elemene or paclitaxel inhibited the growth of MB- 468 cell line. The IC50 and IC20 values treated with β-elemene for 24 h were 34.20 and 52.59 μg/mL and for 48 h were 10.15 and 17.81 μg/mL respectively, while the IC50 values treated with paclitaxel for 24 h and 48 h were 2.449 and 1.698 μg/mL respectively. β-elemene (20 and 40 μg/mL respectively) and Paclitaxel (0.016 and 0.008 μg/mL respectively) synergistically inhibited cell proliferation of MB- 468 cells, with Q value>1.15. β-elemene alone (52.59 μg/mL) apparently decreased the expression of cyclin-B1 protein. The expression of cyclin-B1 protein in the combined group was also lower than that in the PI group (1.698 μg/mL). The expression of P27kip1 was up-regulated when compared with that in the βI group or the PI group. Conclusion β-elemene had synergistic effect with Paclitaxel, and its possible mechanism might be correlated with down-regulating the cell cycle protein cyclin-B1 expression and up-regulating the P27kip1 expression.更多还原