首页|薯蓣皂苷抑制Wnt/β-catenin信号通路促进肝癌细胞凋亡的研究

薯蓣皂苷抑制Wnt/β-catenin信号通路促进肝癌细胞凋亡的研究

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目的 研究薯蓣皂苷(DIO)对人HepG2 肝癌细胞凋亡的影响及其可能抗癌作用机制。方法 DIO(0。25、0。5、1、2、4、6 和 8 μmol/L)干预HepG2 肝癌细胞,MTT法检测细胞增殖情况,并计算半数抑制率(IC50);划痕实验分析细胞的迁移能力,Western blot检查细胞中凋亡因子及Wnt/β-catenin通路蛋白表达差异。结果 与对照组比较,DIO组HepG2 细胞抑制率显著升高(P<0。01),并诱导细胞在形态学上出现凋亡特点,呈时间与剂量依赖性;划痕实验结果显示DIO显著抑制HepG2 细胞的迁移距离;与对照组比较,DIO干预细胞 24h后,Caspase-3、cleaved Caspase-3水平明显上调,而Bcl-2、β-catenin水平显著下调(P<0。05、P<0。01);采用LiCl激活Wnt/β-catenin信号通路,LiCl组细胞中Wnt1、β-catenin水平较对照组显著上调(P<0。01);与LiCl组比较,LiCl+DIO 组HepG2 细胞Wnt1、β-catenin、GSK-3β蛋白表达显著下调(P<0。01)。结论 DIO体外能够促进HepG2 肝癌细胞凋亡,机制可能是其下调β-catenin的蛋白表达,抑制Wnt/β-catenin信号通路传导,进而抑制凋亡因子Bcl-2表达,最终诱导细胞凋亡而发挥抗肝癌作用。
Dioscin promotes apoptosis of HepG2 cells by inhibiting Wnt/β-catenin signaling pathway
Objective To detect the apoptosis effects of dioscin in HepG2 cells and its possible anti-hepatocellular carcinoma mechanisms.Methods HepG2 human hepatocellular carcinoma cells were exposed to 0.25,0.5,1,2,4,6,or 8 μmol/L dioscin,and cell proliferation was measured via MTT assay.The half-maximal inhibitory concentration(IC50)was calculated with the software.A scratch test was used to analyze cell migration ability.Western blot was employed to evaluate the expression of apoptosis and Wnt/β-catenin-pathway-related proteins.Results Compared with the control group,the dioscin-treated HepG2 cells'proliferation was significantly more inhibited,and the inhibition increased in a time-and dose-dependent manner(P<0.01).HepG2 cells showed morphological characteristics of apoptosis after they were treated with 1 μmol/L or 2 μmol/L dioscin.The scratch test indicated that the migration distance of HepG2 cells was remarkably reduced when treated with dioscin.In the Western blot experiment,the expression levels of Caspase-3 and cleaved Caspase-3 were visibility up-regulated,while those of Bcl-2 and β-catenin were significantly down-regulated when the cells were treated with dioscin for 24 h(P<0.05,P<0.01).When LiCl reagent was added to the HepG cells to activate the Wnt/β-catenin signaling pathway,the expression levels of Wnt1 and β-catenin were remarkably increased compared with those of the control group(P<0.01).Compared with the LiCl group,the LiCl+DIO group's expression of Wnt1,β-catenin,and GSK-3β was significantly decreased(P<0.01).Conclusions DIO can promote the apoptosis of HepG2 cells by inhibiting β-catenin protein expression and thereby down-regulating the Wnt/β-catenin signaling pathway.This inhibits apoptosis-related gene Bcl-2 expression,which leads to the induction of cell apoptosis.Therefore,DIO can have an anti-hepatocellular carcinoma effect.

dioscinHepG2hepatocellular carcinomaWnt/β-catenin signaling pathwayapoptosis

梁玉琼、黄庆、黄娟娟、梁芳、滕丽娟、郑洋

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广西中医药大学赛恩斯新医药学院实验中心,南宁 530222

广西中医药大学第一附属医院药学部,南宁 530023

薯蓣皂苷 HepG2 肝癌 Wnt/β-catenin信号通路 细胞凋亡

2022年度广西高校中青年教师科研基础能力提升项目广西自然科学基金项目广西中医药大学赛恩斯新医药学院科研项目

2022KY16712023GXNSFBA0262302023MS004

2024

中国比较医学杂志
中国实验动物学会,中国医学科学院医学实验动物研究所

中国比较医学杂志

CSTPCD北大核心
影响因子:0.473
ISSN:1671-7856
年,卷(期):2024.34(8)