Que Zhongyou, Wang Ping, Hu Yi, Xue Yixue, Liu Xiaobai, Qu Chengbin, Ma Jun, Liu Yunhui
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
Pharmacol Res. 2017 May;119:72-88. doi: 10.1016/j.phrs.2017.01.014. Epub 2017 Jan 19.
Dihydroartemisinin(DHA) is the active metabolic derivative of artemisinin. DHA has potential therapeutic effects on glioma but the detailed mechanism is unclear. In this study, we investigated the role and the underlying mechanisms of DHA in its inhibition of glioma cells. U87 cells are wild-type p53 glioblastoma cells and U251 cells contain mutant p53. DHA inhibited the proliferation, migration and invasion of glioma cells in a dose-dependent manner. DHA promoted reactive oxygen species production and activated p53 in two glioma cell lines, U87 and U251. In U87 cells, DHA significantly up-regulated the expression of p-β-catenin (S45) and inhibited EGFR, β-catenin, p-β-catenin (Y333) and matrix metalloprotease7/9 activity. In U251 cells, DHA significantly up-regulated p-β-catenin (S45), p-β-catenin (Y333) and EGFR, but the expression of β-cateninwas unchanged. We also found that DHA and sh-β-catenin prevented the proliferation of U87 and U251 cells in vivo. In conclusion, DHA inhibited the migration and invasion of human glioma cells with different types of p53 via different pathways.
双氢青蒿素（DHA）是青蒿素的活性代谢衍生物。DHA对胶质瘤具有潜在治疗作用，但其具体机制尚不清楚。在本研究中，我们探究了DHA在抑制胶质瘤细胞中的作用及其潜在机制。U87细胞是野生型p53胶质母细胞瘤细胞，U251细胞含有突变型p53。DHA以剂量依赖方式抑制胶质瘤细胞的增殖、迁移和侵袭。DHA在两种胶质瘤细胞系U87和U251中促进活性氧生成并激活p53。在U87细胞中，DHA显著上调p-β-连环蛋白（S45）的表达，并抑制表皮生长因子受体（EGFR）、β-连环蛋白、p-β-连环蛋白（Y333）和基质金属蛋白酶7/9的活性。在U251细胞中, DHA显著上调p-β-连环蛋白（S45）、p-β-连环蛋白（Y333）和EGFR，但β-连环蛋白的表达未改变。我们还发现，DHA和β-连环蛋白短发夹RNA（sh-β-catenin）在体内可抑制U87和U251细胞的增殖。总之，DHA通过不同途径抑制不同p53类型的人胶质瘤细胞的迁移和侵袭。
