摘要目的 研究双氢青蒿素(DHA)抑制胶质瘤生长作用、机制及联合替莫唑胺(TMZ)的协同抗肿瘤作用.方法 选用胶质瘤细胞株10个,MTT法检测DHA持续作用72 h后细胞株半数抑制浓度( IC50)；0.5 μg/ml浓度DHA联合梯度浓度TMZ作用于SKMG -4细胞株,MTT法检测IC50；MDC法荧光分析DHA作用后自噬泡形成；梯度浓度DHA作用SKMG -4,Western Blot法检测caspase -3、Beclin-1、LC3-B蛋白表达.结果 DHA抑制胶质瘤细胞生长IC50为(1.17±0.078) μg/ml ～ (23.568±0.796) μg/ml；在SKMG -4细胞株中,DHA实验组与空白对照相比,可见明显的自噬泡染色；Beclin-1及LC3 -B表达随DHA浓度增加而增加,而caspase -3表达无明显变化；DHA联合TMZ抑制SKMG-4生长,IC50值明显下降(P＜0.01).结论 DHA具有抗胶质瘤活性,诱导胶质瘤细胞自噬；DHA联合作用可提高TMZ的抗胶质瘤SKMG -4活性,机制可能为增强了TMZ自噬效能.

abstractsObjective To investigate the anti -glioma efficacy of dihydroartemisinin (DHA) and combined with temozolomide (TMZ) on human glioma cell line in vitro.Methods The growth inhibition of DHA on 10 glioma cell lines induced by DHA treatment for 72 h was analyzed by MTT method.TMZ combined with 0.5 μg/ml DHA,and the IC5o value was measured in SKMG -4 cells.The autofluorescent drug monodansylcadaverine (MDC) was used to mark autophagicvacuoles.The autophagy related protein LC3 - B and Beclin - 1,and the apoptosis protein caspase - 3 were analyzed by western blot (WB).Results The IC50 of DHA was different in ten glioma cell lines [ from ( 1.17 ± 0.078 ) μg/ml to (23.568±0.796) μg/ml].In SKMG -4 cells,the autophagicvacuoles were detected in the DHA group,the IC50 of TMZ had significant difference with 0.5 μg/ml DHA contrast to the control group ( P ＜ 0.01 ),and the levels of LC3 - B and Beclin - 1 protein were increased gradually with the increase of DHA concentration,and caspase -3 protein has no difference.Conclusion DHA can inhibit proliferation of glioma cell lines and increase the efficacy of TMZ,and the autophagy may be the mechanism.