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目的探讨18β-甘草次酸(GA)通过Wnt/β-catenin信号对人类白血病细胞株U937细胞凋亡的调控机制。方法用双荧光素酶报告基因检测Wnt经典信号通路信号,用四甲基偶氮唑蓝法检测细胞增殖,Annex in V/PI双标法检测凋亡率及坏死率,Western-blot检测凋亡及坏死相关蛋白水平。结果 18β-甘草次酸能增强Wnt/β-catenin信号通路的β-catenin/TCF活性,从而上调该信号通路靶蛋白CyclinD1的表达;并通过上调促凋亡蛋白BAX的表达,下调抗凋亡蛋白Mcl-1、Bcl-2和坏死蛋白RIP3的蛋白表达水平,同时增强caspase3活性,从而诱导细胞凋亡,且在一定范围内呈剂量依赖性。结论 18β-甘草次酸通过激活Wnt/β-catenin信号通路来抑制U937细胞增殖和诱导其凋亡,并且对细胞的坏死没有促进作用。
Objective To investigate the regulatory mechanism of 18β-glycyrrhetinic acid (GA) on the apoptosis of human leukemia cell line U937 by Wnt / β-catenin signaling. Methods Dual luciferase reporter gene was used to detect the signal transduction pathway of Wnt. Cell proliferation was detected by MTT method. Apoptosis rate and necrosis rate were detected by Annexin V / PI double-labeled method. Apoptosis was detected by Western-blot And necrosis related protein levels. Results 18β-glycyrrhetinic acid could enhance the β-catenin / TCF activity of Wnt / β-catenin signaling pathway and up-regulate the expression of CyclinD1, a target protein of Wnt / β-catenin signaling pathway. By up-regulating the expression of pro-apoptotic protein BAX, The expression of Mcl-1, Bcl-2 and RIP3 protein in the necrotic tissue were increased, and the activity of caspase 3 was also increased. The apoptosis of cells was induced and dose-dependent. Conclusion 18β-glycyrrhetinic acid inhibits the proliferation and induces apoptosis of U937 cells by activating the Wnt / β-catenin signaling pathway and has no effect on cell necrosis.