南方医科大学学报2017，Vol.37Issue(7)：883-888,6.DOI:10.3969/j.issn.1673-4254.2017.07.05
抑制单羧酸转运蛋白1可增强鼻咽癌细胞HNE1/DDP对顺铂诱导凋亡的敏感性
Small interfering RNA-mediated monocarboxylate transporter 1 silencing enhances sensitivity of nasopharyngeal carcinoma HNE1/DDP cells to cisplatin-induced apoptosis
摘要
Abstract
Objective To investigate the effect of small interfering RNA (siRNA)-mediated silencing of monocarboxylate transporter 1 (MCT1) on the sensitivity of drug-resistant nasopharyngeal carcinoma HNE1/DDP cells to cisplatin (DDP)-induced apoptosis and explore the possible mechanism. Methods The expression of MCT1 was analyzed in HNE1 and HNE1/DDP cells and in HNE1/DDP cells transfected with siRNA using Western blot. MTT assay was used to assess the inhibitory effect of different concentrations of DDP alone or in combination with MCT1 siRNA on the proliferation of HNE1/DDP cells. The apoptosis of cells treated with MCT1 siRNA or/and DDP (8μmol/L) was assessed using flow cytometry with PI staining, and the mitochondrial membrane potential was detected using JC-1 staining assay; the expressions of Mcl-1, Bak, Bcl-2, and Bax were analyzed using Western blotting. Results HNE1/DDP cells showed a high expression of MCT1, and MCT1 silencing using siRNA significantly increased the sensitivity of HNE1/DDP cells to DDP (P<0.05) and partly reversed DDP resistance of the cells. MCT1 silencing enhanced the sensitivity of HNE1/DDP cells to DDP-induced apoptosis. Treatment of HNE1/DDP cells with MCT1 siRNA combined with 8 μmol/L DDP for 24 h resulted in an apoptotic rate of (51.23 ± 2.86)%, significantly higher than that in cells treated with MCT1 siRNA or DDP alone (P<0.05). The combined treatment also reduced the mitochondrial membrane potential, down-regulated the expression of Mcl-1 and Bcl-2, and up-regulated the expression of Bax in the DDP-resistant cells. Conclusion MCT1 siRNA can enhance the sensitivity of HNE1/DDP cells to DDP-induced apoptosis, the mechanism of which may involve the down-regulation of Mcl-1 and Bcl-2 and up-regulation of Bax expression.关键词
鼻咽癌细胞/顺铂/耐药性/单羧酸转运蛋白1/小干扰RNAKey words
nasopharyngeal carcinoma/cisplatin/drug resistance/monocarboxylate transporter 1/small interfering RNA引用本文复制引用
张配,刘芳,高娇,马琳艳,孙小锦,郑海伦,刘浩,赵素容..抑制单羧酸转运蛋白1可增强鼻咽癌细胞HNE1/DDP对顺铂诱导凋亡的敏感性[J].南方医科大学学报,2017,37(7):883-888,6.基金项目
国家自然科学基金(81603155) （81603155）
安徽省自然科学基金青年基金(1708085QH212) （1708085QH212）
安徽省高校省级自然科学研究项目(KJ2015B001by, KJ2015A177,KJ2016A486) （KJ2015B001by, KJ2015A177,KJ2016A486）
蚌埠医学院自然科学基金重点项目(BYKY1606ZD) Supported by National Natural Science Foundation of China (81603155). （BYKY1606ZD）
