白藜芦醇调控Wnt/β-catenin信号通路抑制胶质瘤细胞的机制

Mechanism of resveratrol in inhibiting glioma cells by regulating Wnt/β-catenin signaling pathway

目的分析白藜芦醇通过调控Wnt/β-catenin信号通路抑制胶质瘤细胞的机制。方法采用0(对照组)、25(低剂量组)、50(中剂量组)以及100μmol/L(高剂量组)白藜芦醇对胶质瘤细胞U251进行处理,比较各组细胞培养24、48以及72 h时的细胞活力、侵袭个数、迁移个数、凋亡率,比较各组细胞培养72 h时的Wnt3a、β-catenin蛋白表达及mRNA水平。结果与对照组相比,各白藜芦醇培养组细胞培养24、48以及72 h时细胞活力均降低,细胞侵袭、迁移个数均减少,细胞凋亡率均升高,且各白藜芦醇培养组细胞活力随培养时间的延长而逐渐降低,细胞侵袭、迁移个数均随培养时间的延长而增加,细胞凋亡率均随培养时间的延长而增加(P<0.05);各培养时间下,白藜芦醇培养低剂量组的细胞活力均最高、细胞侵袭和迁移个数均最多、细胞凋亡率均最低,而高剂量组细胞活力最低、细胞侵袭和迁移个数均最少、细胞凋亡率均最高,差异均有统计学意义(P<0.025);培养72 h时,与对照组比较,各白藜芦醇培养组细胞Wnt3a、β-catenin蛋白表达及mRNA水平均降低,且低剂量组的细胞Wnt3a、β-catenin蛋白表达及mRNA水平最高,高剂量组最低,差异有统计学意义(P<0.05)。结论白藜芦醇可能通过抑制Wnt/β-catenin信号通路抑制胶质瘤细胞活性,减少细胞侵袭和迁移,促进细胞凋亡。

Objective To explore the mechanism of resveratrol in inhibiting glioma cells by regulating the Wnt/β-catenin signaling pathway.Methods Glioma cells(U251)were treated with resveratrol and divided into at the following groups based on the concentrations of resveratrol:0μmol/L(control group),25μmol/L(low dose group),50μmol/L(medium dose group)and 100μmol/L(high dose group).Cell viability,invading cell numbers,migrating cell numbers and apoptosis rates were compared at 24 h,48 h,and 72 h among above groups.Both protein and mRNA expression levels of Wnt3a andβ-catenin were compared at 72 h after the treatment among these groups.Results When compared to control group at 24 h,48 h,and 72 h after the treatment,cell viability was decreased,and the numbers of invading cells and migrating cells were reduced in low-,medium-and high-dose groups,while apoptotic rates were increased.In addition,cell viability was decreased in a time-dependent manner,while the numbers of invasive cells and migrating cells as well as apoptotic rates were increased over the time(P<0.05).At 24 h,48 h,and 72 h,low dose group had the highest cell viability,the highest number of invading cells and migrating cells and the lowest apoptotic rate among resveratrol-treated groups,contrary to high dose group.The difference was significant(P<0.025).When compared to control group at 72 h after the treatment,both protein and mRNA levels of Wnt3a andβ-catenin were reduced in low-,medium-and high-dose groups.Low-dose group had the highest protein and mRNA levels of Wnt3a andβ-catenin among resveratrol-treated groups,contrary to high dose group.The difference was significant(P<0.025).Conclusion Resveratrol can impair glioma cell viability by inhibiting the Wnt/β-catenin signaling pathway,reducing cell invasion,and migration and promoting cellular apoptosis.