青蒿素及其衍生物对恶性胶质瘤的放射增敏的实验-第三军医大学学报.DOC

青蒿琥酯增加人脑胶质瘤细胞CHG-5对β射线的敏感性 董俊清1，赵妍妍1，姚琦1，蒋为薇1，李军1，李斌1，庞学利2，周红1, * （第三军医大学：1药学院药理教研室，重庆 400038，2西南医院肿瘤科，重庆 400038） 摘要： 目的 从青蒿素及其衍生物中筛选出对人脑胶质瘤细胞CHG-5及U87具有较好放射增敏效果的药物，并初步探讨其放射增敏机制。关键词Artesunate enhances the radiosentivity of human glioma cell line CHG-5 toβ-ray DONG Jun-qing1,ZHAO Yan-yan1,YAO Qi1,JIANG Wei-wei1,LI Jun1,LI Bin1,PANG Xue-li2,ZHOU Hong1,* (1Department of Pharmacology, College of Pharmacy,Third Millitary Medical University,Chongqing 400038;2Department of Oncology,Southwest Hospital, Third Millitary Medical University,Chongqing 400038) Abstract： Objective To assay the cytotoxicity of artemisinin(ART), dihydroartemisinin (DHA) and artesunate(AS) to two glioma cell lines CHG-5 and U87. We selected a compound which had radiosensitization on both cell lines when synergied with β-ray. Also, we observed the radiosentivity in vitro and investigated the mechanism preliminarily. Methods First, we employed MTT to assay the IC50s of two cell lines to ART and its derivatives. When synergized withβ-ray, we observed the radiosensitization of drugs with 20% IC50 and selected the optimal one. Subsequently, sensitivity enhancement ratio(SER) was determined by colony-forming assay. Scratch test was used to observe the effect of objective drug on cell migration. Then, intracellular reduced GSH was measured. Finally, flow cytometry was employed to assay the cell apoptosis and cell cycle distribution. Results For CHG-5, the IC50 of ART, DHA and AS was 1.47mmol/l, 0.20mmol/l and 0.29mmol/l, respectively. Correspondingly, the IC50 for U87 was 1.61mmol/l, 0.25mmol/l and 0.46mmol/l, respectively. Only AS could suppress the proliferation of both cell lines under the concentration of 20% IC50 when combined withβ-ray. Furthermore，the SER of 0.06 mmol/l AS for CHG-5 was 1.25. Meanwhile, 0.06 mmol/l AS could significantly inhibit the cell migration. Compared with medium group, down-regulated GSH production was found after the treatment of 0.06 mmol/l AS（P＜0.05）. Flow cytometry sug