抑制miR-23a表达增强卵巢癌顺铂敏感性的分子机制  

Inhibition of micro RNA-23a increases cisplatin sensitivity of ovarian cancer cells: the possible molecular mechanisms

作　　者：金爱红[1] 周霞平[1] 周凤珍[1] 

机构地区：[1]深圳市第二人民医院妇科,广东深圳518035

出　　处：《南方医科大学学报》2015年第1期125-128,共4页Journal of Southern Medical University

摘　　要：目的分析抑制mi R-23a表达后,耐药卵巢癌A2780细胞对化疗药物顺铂的敏感性变化及其分子机制。方法选择顺铂耐药卵巢癌A2780细胞株为研究样本,并分为两组,其中对照组仅加入顺铂,实验组加入顺铂及antagomir-23a。应用MTT法检测antagomir-23a抑制mi R-23a并经顺铂处理后细胞增殖抑制率;应用流式细胞仪分析细胞周期分布情况;应用Hoechst33258染色分析细胞凋亡形态学变化;应用Western blot法分析耐药糖蛋白P-gp的表达变化。结果抑制mi R-23a并经顺铂处理后,细胞增殖抑制率显著上升(P<0.01),顺铂中效浓度(IC50)为17.89μmol/L,比对照组IC50110.18μmol/L降低了83.76%(P<0.01),细胞被阻滞于G0/G1期且凋亡率增加(P<0.01);Hoechst33258染色见细胞核浓缩、染色增强。Western blot检测提示细胞P-gp蛋白表达随着顺铂浓度加大而逐渐减低(P<0.01)。结论抑制耐药卵巢癌A2780细胞内mi R-23a表达后,细胞对顺铂的敏感性显著增加,这可能mi R-23a靶基因负性调控因素得以缓解,并由此引发P-gp蛋白表达受抑有关。Objective To investigate the changes in cisplatin sensitivity of resistant ovarian cancer A2780 cells after inhibition of mi R- 23 a expression and explore the molecular mechanisms. Methods The drug- resistant ovarian cancer A2780 cells were exposed to cisplatin alone or in combination with antagomir- 23 a. The cell inhibition rates after the treatments were detected using MTT assay, cell cycle changes assessed with flow cytometry, and apoptotic cells observed using Hoechst33258 staining.The changes in glycoprotein P-gp expression in the cells were detected using Western blotting. Results Inhibition of mi R-23 a combined with cisplatin treatment significantly increased the cell inhibition rate（P〈0.01） and lowered the IC50 of cisplatin by83.76% from 110.18 μmol/L in the control group to 17.89 μmol/L（P〈0.01）. The combined treatments also caused cell cycle arrest in G0/G1 phase, increased the cell apoptosis rate（P〈0.01） and the number of cells stained with Hoechst33258; the cellular expression of P- gp protein was significantly reduced as the cisplatin doses increased（P〈0.01）. Conclusion Inhibition of mi R-23 a expression increases the sensitivity of A2780 cells to cisplatin possibly by inhibiting the negative regulation by mi R- 23 a target genes that causes inhibition of P-gp protein expression.

关 键 词：微小RNA 顺铂 卵巢癌 耐药性 

分 类 号：R737.31[医药卫生—肿瘤]