雷帕霉素抑制mTOR活性诱导细胞的生长和下调EBV^+人鼻咽癌细胞HIF-1α介导的VEGF表达  

mTOR inhibition impacts cell viability and downregulates expression of HIF-1α-mediated VEGF in EBV-positive human nasopharyngeal carcinoma cells

作　　者：任源[1] 黄建鸣[1] 查晓[1] 邓碧芳[1] 郎锦义[1] 

机构地区：[1]四川省肿瘤医院,四川成都610041

出　　处：《华西药学杂志》2013年第1期50-52,共3页West China Journal of Pharmaceutical Sciences

基　　金：四川省科技厅科研基金项目(编号:2008JY0020)

摘　　要：目的观察雷帕霉素(Rap)体外对人鼻咽癌HNE-1EBV+和CNE-1EBV-细胞乏氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)表达的影响及生长抑制作用。方法采用MTT法检测Rap作用72 h IC50;用RT-PCR和ELISA分别测定Rap作用24 h后,细胞HIF-1αmRNA和培养上清液中VEGF的表达水平。结果 Rap呈剂量依赖性地抑制HNE-1EBV+和CNE-1EBV-细胞的生长,IC50分别为43.9、41.7μmol.L-1;Rap使HNE-1EBV+细胞HIF-1αmRNA和VEGF表达水平分别下调了24%、55%,但对CNE-1EBV-细胞无明显影响。结论 Rap对两株鼻咽癌细胞具有相当的生长抑制作用,可显著下调HNE-1EBV+细胞HIF-1α介导的VEGF表达,提示Rap对于改善EBV+鼻咽癌的治疗预后具有潜在的作用。OBJECTIVE To study the effect of mTOR inhibition on cell viability,HIF-1α and VEGF expression in human nasopharyngeal carcinoma HNE-1 EBV＋ and CNE-1 EBV-cells.METHODS Growth inhibition effect of rapamycin on HNE-1 and CNE-1 cells was assessed by MTT assay.The levels of HIF-1α mRNA and VEGF after 24 h were determined by reverse transcription-polymerase chain reaction（RT-PCR） and Enzyme-linked immunosorbent assay（ELISA）,respectively.RESULTS The growth of HNE-1 and CNE-1 cells was inhibited significantly by rapamycin dose-dependently and IC50 values for HNE-1 and CNE-1 cells cultured with rapamycin for 72 hours were 43.9 μmol·L-1 and 41.7 μmol·L-1,respectively;RT-PCR showed that rapamycin significantly downregulated mRNA expression of HIF-1α and levels of VEGF in HNE-1 cells but not in CNE-1 cells.CONCLUSIONS mTOR inhibition not only can suppress the growth of HNE-1 and CNE-1 cells and significantly downregulate the HIF-1α-mediated expression of VEGF in HNE-1 cells,but also have a potential role for improvement in prognosis of EBV＋ nasopharyngeal carcinoma.

关 键 词：雷帕霉素 哺乳动物雷帕霉素靶蛋白 鼻咽癌 乏氧诱导因子1Α 血管内皮生长因子 EB病毒 

分 类 号：R96[医药卫生—药理学]