双氢青蒿素通过阻断Wnt/β-catenin信号抑制骨肉瘤细胞系体外增殖和侵袭  

Dihydroartemisinin(DHA) inhibits proliferation and invasion of osteosarcoma cell line in vitro by suppressing Wnt/β-catenin signaling

作　　者：王文娟[1] 赵丹[1] 徐静[1] 李丽[1] 董谦[1] 王玉凤[1] 冯巧灵[1] 王锦[1] 何娟文[1] 何通川[1] 罗进勇[1] 

机构地区：[1]重庆医科大学检验医学院检验医学教育部重点实验室重庆市重点实验室,重庆400016

出　　处：《基础医学与临床》2014年第8期1017-1022,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(31071304;81272006);973子课题(2011CB707906)

摘　　要：目的研究双氢青蒿素(DHA)在体外对骨肉瘤细胞增殖和侵袭的抑制作用及其可能的分子机制。方法不同浓度的DHA处理骨肉瘤细胞,结晶紫染色检测细胞增殖。Western blot和荧光素酶报告基因实验检测Wnt/β-catenin信号通路的活化情况。结果 DHA在体外能明显浓度依赖性地抑制人骨肉瘤细胞的增殖和侵袭(P<0.05);DHA可降低骨肉瘤细胞β-catenin的蛋白水平和转录调控活性(P<0.01),过表达β-catenin可逆转DHA对骨肉瘤细胞增殖和侵袭的抑制作用(P<0.05),而β-catenin基因沉默则可进一步加强其抑制效果(P<0.01)。结论DHA可明显抑制人骨肉瘤细胞增殖和侵袭,这种作用可能与其阻断Wnt/β-catenin信号通路相关。Objective To investigate the proliferation and invasion inhibitory effect of dihydroartemisinin （DHA） on human osteosareoma （OS） cells and the possible molecular mechanism involved. Methods OS cells were seeded and treated with different concentrations of DHA. Cells were stained with crystal violet to find cell viability. ECM Transwell assay was used to assess the alteration in cellular invasion induced by DHA in OS cells. Western blot and luciferase assay were used to evaluate activation of Wnt/β-catenin signal pathway. Results DHA can inhibit proliferation and reduce invasion in human OS cells. Total protein and transcription activity of β-catenin in OS cells were reduced by DHA treatment. Moreover, the inhibitory effect of DHA on OS cells was reversed by over-expression of β-catenirt, but was further enhanced by know-down of β-catenin, respectively. Conclusions Our results showed that DHA can inhibit tumor proliferation and invasion of OS cells by inactivating Wnt/β-catenin signaling.

关 键 词：双氢青蒿素 骨肉瘤 WNT β-catenin 信号通路 

分 类 号：R738.1[医药卫生—肿瘤]