Objective To investigate the effect of Wnt signaling pathway inhibitor combined with ursolic acid on the proliferation and ap-optosis of acute leukemia cells. Methods The acute leukemia cell U937 after the action of ursolic acid at different concentrations,cell prolifera-tion was detected by MTT,calculated median inhibitory concentration. U937 cells were divided into control group,ursolic acid group,inhibitor group and combined group,the cells of combined group were treated with half inhibitory concentrations of ursolic acid and Wnt signaling pathway inhibitor FH - 535,and the ursolic acid group was treated with a half inhibitory concentration of ursolic acid,the inhibitor group was treated with the Wnt signaling pathway inhibitor FH - 535,cell proliferation was detected by MTT,apoptosis was detected by flow cytometry,the levels of Cleaved Caspase - 3,β - catenin and c - myc protein were detected by Western blot. Results The survival rate of U937 cells decreased after 0, 4,8,16 and 32 μmol/ L ursolic acid action. The cell viability,the levels of β - catenin and c - myc in the ursolic acid group,the inhibitor group and the combined group were significantly lower than those in the control group,The rate of apoptosis and the level of Cleaved and Caspase - 3 were significantly higher than those of the control group,the difference were statistically significant (P < 0. 05). The cell viability,the levels ofβ - catenin and c - myc in the combined group were significantly lower than those in the ursolic acid group and the inhibitor group,the apoptotic rate and the level of Cleaved Caspase - 3 were significantly higher than that of the ursolic acid group and the inhibitor group,the difference were statistically significant (P < 0. 05). Conclusion Both the use of ursolic acid and Wnt signaling pathway inhibitors can inhibit the proliferation of leukemia cells,promote apoptosis of leukemia cells,furthermore,the combination of ursolic acid and Wnt signaling pathway inhibitors has a greater inhibitory effect on leukemia cell proliferation and apoptosis.%目的 采用前瞻性研究探讨熊果酸联合Wnt信号通路抑制剂对急性白血病细胞增殖和凋亡的影响.方法 用不同浓度的熊果酸作用急性白血病细胞U937后,噻唑蓝(MTT)检测细胞增殖,计算半数抑制浓度.U937细胞分为对照组、熊果酸组、抑制剂组和联合组,联合组细胞用半数抑制浓度的熊果酸和Wnt信号通路抑制剂FH-535共同处理,熊果酸组用半数抑制浓度的熊果酸处理,抑制剂组用Wnt信号通路抑制剂FH-535处理,MTT检测细胞增殖,流式细胞术检测细胞凋亡,Western blot检测活化的含半胱氨酸的天冬氨酸蛋白水解酶3(Cleaved Caspase-3)、β-连环蛋白(β-catenin)、Wnt信号通路下游靶基因(c-myc)蛋白水平.结果 0、4、8、16、32μmol/L的熊果酸作用后的U937细胞存活率依次降低.熊果酸组、抑制剂组、联合组细胞存活率、β-catenin和c-myc表达水平明显低于对照组,而细胞凋亡率和Cleaved Caspase-3水平明显高于对照组,差异具有统计学意义(P<0.05).联合组细胞存活率、β-catenin和c-myc表达水平明显低于熊果酸组和抑制剂组,而凋亡率和Cleaved Caspase-3水平明显高于熊果酸组和抑制剂组,差异具有统计学意义(P<0.05).结论 单纯使用熊果酸或者Wnt信号通路抑制剂均能够抑制白血病细胞增殖,促进急性白血病细胞凋亡,并且熊果酸和W n t信号通路抑制剂联合使用对白血病细胞增殖抑制作用和凋亡促进作用更大.
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