MLN4924对紫杉醇耐药的前列腺癌细胞增殖和凋亡的影响

Effects of MLN4924 on the proliferation and apoptosis of paclitaxel-resistant prostate cancer cells

目的:研究MLN4924对紫杉醇耐药的前列腺癌细胞增殖和凋亡的影响,从而为紫杉醇耐药前列腺癌的临床治疗提供新的理论依据。方法:不同浓度的MLN4924作用紫杉醇耐药的前列腺癌细胞PC3-TxR和DU145-TxR 48和72小时后,采用MTS检测细胞活力。Western blot检测凋亡相关蛋白Caspase-3、CDT1、p27以及EMT标志物水平。结果:MLN4924能够显著抑制PC3-TxR和DU145-TxR细胞的增殖,并且具有时间和浓度的依懒性。Western blot结果显示MLN4924作用后显著增加细胞内凋亡相关蛋白Caspase-3、CDT1和p27的表达。结论:MLN4924能够显著抑制紫杉醇耐药的前列腺癌细胞增殖、促进细胞凋亡,其相关机制为MLN4924可通过上调p27蛋白表达促进紫杉醇耐药的前列腺癌细胞凋亡。

Objective:To study the effect of MLN4924 on the proliferation and apoptosis of paclitaxel-resistant prostate cancer cells.So as to provide a new theoretical basis for the clinical treatment of paclitaxel resistance prostate cancer.Methods:Paclitaxel resistance prostate cancer cells PC3-TxR and DU145-TxR were treated with different concentrations of MLN4924 for 48 and 72 h and cell viability was determined by MTS assay.The protein expression of the associated proteins in cell apoptosis,including Caspase-3,CDT1,p27 and EMT markers was determined by Western blot.Results:The proliferation of PC3-TxR and DU145-TxR cells significantly decreased with the concentration of MLN4924 increased in a dose and time dependent manner.The results of Western blot showed the protein expression of the associated apoptosis proteins including Caspase-3,CDT1 and p27 was higher after MLN4924 treated.Conclusion:MLN4924 significantly inhibited the proliferation and induced apoptosis in paclitaxel resistance cells.The related mechanism is that MLN4924 can promote paclitaxel-resistant prostate cancer cell apoptosis by up-regulating p27 protein expression.