紫杉醇增强HeLa细胞对顺铂的敏感性及机制研究

Paclitaxel Enhances the Sensitivity of HeLa Cell to Cisplatin and its Mechanism

目的探讨紫杉醇增强HeLa细胞对顺铂的敏感性及机制研究。方法将细胞分为对照组,顺铂组,紫杉醇组,顺铂+紫杉醇联合组。MTT法检测细胞活力,流式细胞术分别检测细胞凋亡及细胞周期,Western blot检测细胞周期蛋白D1(Cyclin D1)、Cyclin E、细胞周期蛋白依赖性激酶抑制剂p21、p27蛋白表达及磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)信号通路激活情况。结果与对照组比较,顺铂组、紫杉醇组及联合组细胞活力降低(P<0.01),细胞凋亡率提高(P<0.01),细胞周期阻滞在G1期(P<0.01),Cyclin D1及Cyclin E表达量下调(P<0.01),p21及p27表达量上调(P<0.01),PI3K及p-AKT表达量下调(P<0.01)。与顺铂组及紫杉醇组比较,联合组细胞活力降低(P<0.01),细胞凋亡率提高(P<0.01),细胞周期阻滞在G1期(P<0.01),Cyclin D1及Cyclin E表达量下调(P<0.01),p21及p27表达量上调(P<0.01),PI3K及p-AKT表达量下调(P<0.01)。结论紫杉醇、顺铂单独或联合给药均能显著抑制HeLa细胞增殖,诱导细胞凋亡,且具有协同作用。

Objective This study was to explore that paelitaxel enhanced the sensitivity of HeLa cell to eisplatin as well as the mechanism. Methods HeLa cells were divided into eontrol group, eisplatin group, paelitaxel group and paelitaxel plus eisplatin group. The cell viability was measured by MTT assay-. The cell apoptosis and cell cycle were detected by flow eytometry. The expression of CyelinD1, CyelinE, eyelin dependent kinase inhibitor p21, p27 protein and activation of phosphatidylinositol 3 kinase / protein kinase B （PI3K/AKT） signal pathway were assayed by Western blot. Results Compared with control group, the cell viability was reduced （P 〈 0.01）, apoptotie rate increased （P 〈 0.01）, cell cycle arrested in GI phase （P 〈 0.01）, the CyelinD1 and CyelinE expression down-regulated （P 〈 0.01）, the p21 and p27 expression upreg- ulated （P 〈 0.01）, and the PI3K and p-AKT expression decreased （P 〈 0.01） in eisplatin group and paelitaxel group. Compared with eisplatin group and paelitaxel group, the cell viability was reduced （P 〈 0.01）, cell early apoptotie rate and late apoptotie rate increased （P 〈 0.01）, cell cycle arrested in GI phase （P 〈 0.01）, expression of CyelinD 1 and CyelinE down-regulated （P 〈 0.01）, expression of p21 and p27 up-regulated （P 〈 0.01）, expression of PI3K and p-AKT decreased （P 〈 0.01） in eisplatin and paelitaxel combined group. Conclusion Paelitaxel/eisplatin alone or in combination could inhibit the proliferation of HeLa cell and induce its apoptosis, and they have synergistic effects.