王远政;田晓滨;刘洋;刘曦明;张一;舍荣峰;

• 1:贵州省人民医院骨科
• 2:重庆医科大学附属第二医院骨科
• 3:广州军区武汉总医院骨科

摘要(Abstract)：

[目的]研究冬凌草甲素(oridonin,ORI)对人骨肉瘤143B细胞增殖的抑制作用与Wnt/β-catenin信号的关系。[方法]结晶紫染色法及Western blot研究ORI对143B细胞增殖的抑制作用;流式细胞术及Western blot检测ORI诱导143B细胞凋亡的作用;通过β-catenin/Tcf4荧光素酶报告质粒检测ORI对Wnt/β-catenin信号活性的影响;Western blot和RT-PCR分析ORI对Wnt/β-catenin信号相关因子β-catenin、Dickkopf1(Dkk1)、糖原合成酶激酶3β(glycogen synthase kinase 3β,GSK3β)及p-GSK3β表达水平的影响;最后,采用外源性过表达β-catenin和Dkk1以及沉默β-catenin研究ORI抑制143B细胞增殖与Wnt/β-catenin的关系。[结果]与对照组比较,ORI能明显抑制143B细胞增殖(P<0.05),下调增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)蛋白表达;ORI能显著诱导细胞凋亡、上调caspase3表达并将细胞周期阻滞在G1期;ORI能明显抑制细胞中β-catenin/Tcf4的转录活性;ORI对β-catenin的mRNA表达无影响,但能上调Dkk1的mRNA表达;ORI能增加Dkk1和GSK3β蛋白表达,并降低GSK3β磷酸化水平和β-catenin蛋白水平;外源性过表达β-catenin能减弱ORI抑制143B细胞增殖的作用,而过表达Dkk1和沉默β-catenin能增强ORI抑制143B细胞增殖的作用。[结论]ORI能抑制人骨肉瘤143B细胞的增殖并诱导其凋亡,该作用可能与抑制Wnt/β-catenin信号活性相关;而ORI抑制Wnt/β-catenin信号活性则可能与激活GSK3β和Dkk1活性有关。

关键词(KeyWords)： 冬凌草甲素;Wnt/β-catenin信号;骨肉瘤;增殖抑制;细胞凋亡

Abstract:

Keywords:

基金项目(Foundation): 贵州省科技厅基金资助项目(项目编号:LH[2015]7122)

作者(Author): 王远政;田晓滨;刘洋;刘曦明;张一;舍荣峰;

Email:

DOI:

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