ART调节PI3K/AKT通路对肝癌细胞增殖及迁移的影响  

Effect of artesunate regulating ARTPI3K/Akt pathway on proliferation and migration of hepatocellular carcinoma cells

作　　者：张雄[1] 周江 李涛[1] 郝琪伟[1] 李胜[1] 杨刚 李腾 李建雄 乔培宇 张鑫[1] ZHANG Xiong;ZHOU Jiang;LI Tao;HAO Qi-wei;LI Sheng;YANG Gang;LI Teng;LI Jian-xiong;QIAO Pei-yu;ZHANG Xin(WardⅡ,Department of General Surgery,Yulin Second Hospital,Yulin 719000,Shaanxi,CHINA)

机构地区：[1]榆林市第二医院普通外科二病区,陕西榆林719000

出　　处：《海南医学》2023年第15期2129-2134,共6页Hainan Medical Journal

基　　金：陕西省榆林市科协青年人才托举计划项目(编号:20190107)。

摘　　要：目的探究青蒿琥酯(artesunate,ART)调节磷脂酞肌醇3-激酶/蛋白激酶B(PI3K/AKT)信号通路对肝癌细胞增殖及迁移的影响。方法体外培养HepG2细胞,分为对照组以及不同浓度(30μg/mL、60μg/mL和120μg/mL)ART组。比较不同组别HepG2细胞的细胞增殖率、细胞迁移数量、侵袭数量以及Ki-67蛋白、凋亡相关蛋白(Bax、Bcl-2、Caspase-3)、基质金属蛋白酶2(MMP2)、MMP9和PI3K/AKT通路相关蛋白[磷脂酞肌醇3-激酶(PI3K)、磷酸化的磷脂酞肌醇3-激酶(p-PI3K)、磷酸化的蛋白酶B(p-AKT)]的表达水平。结果不同浓度ART作用于HepG2细胞后,30μg/mL组、60μg/mL组和120μg/mL组的细胞增殖率分别为(81.73±8.39)%、(65.26±6.48)%、(44.27±4.66)%,Ki-67蛋白表达分别为0.76±0.11、0.43±0.09、0.29±0.04,分别与对照组的(100.00±10.51)%、0.98±0.16比较均明显降低,且ART浓度越高,细胞增殖率和Ki-67蛋白表达越低,差异均有统计学意义(P<0.05);不同浓度ART作用于HepG2细胞后,30μg/mL组、60μg/mL组和120μg/mL组的细胞凋亡率分别为(24.84±4.91)%、(36.02±7.35)%、(50.27±10.02)%,Bax蛋白表达分别为0.26±0.05、0.39±0.06、0.58±0.08,Bcl-2蛋白表达分别为0.62±0.07、0.48±0.06、0.33±0.04,Caspase-3蛋白表达分别为10.26±0.68、12.47±0.77、14.96±0.81,分别与对照组的(5.75±1.63)%、0.17±0.03、0.83±0.09、8.73±0.46比较,细胞凋亡率、Bax和Caspase-3蛋白表达明显升高,Bcl-2表达明显降低,且ART浓度越高,细胞凋亡率、Bax和Caspase-3蛋白表达越高,Bcl-2表达越低,差异均有统计学意义(P<0.05);不同浓度ART作用于HepG2细胞后,30μg/mL组、60μg/mL组和120μg/mL组的细胞迁移数量分别为(189.11±16.73)个、(162.29±15.03)个、(134.26±13.26)个,细胞侵袭数量分别为(144.13±13.46)个、(121.61±10.23)个、(90.26±8.71)个,MMP2蛋白表达分别为0.46±0.08、0.38±0.06、0.29±0.05,MMP9蛋白表达分别为0.41±0.09、0.33±0.06、0.24±0.03,分别与对照组的(234.28±20.64)个、(187Objective To research the effect of artesunate(ART)regulating phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway on the proliferation and migration of hepatocellular carcinoma cells.Methods HepG2 cells were cultured in vitro and divided into control group and ART group with different concentrations(30μg/mL,60μg/mL,and 120μg/mL).The cell proliferation rate,cell migration number,invasion number of HepG2 cells,and Ki-67 protein,apoptosis-related proteins(Bax,Bcl-2,Caspase-3),matrix metalloproteinase-2(MMP-2),MMP9,and PI3K/AKT pathway-related proteins[phosphoinositide 3-kinase(PI3K),phosphoinositide 3-kinase(p-PI3K),and phosphoprotease B]were compared among the four groups.Results After different concentrations of ART were applied to HepG2 cells,the cell proliferation rates of 30μg/mL group,60μg/mL group,and 120μg/mL group were(81.73±8.39)%,(65.26±6.48)%,and(44.27±4.66)%,respectively,and the expression levels of Ki-67 protein were 0.76±0.11,0.43±0.09,and 0.29±0.04,respectively,which were all significantly lower than(100.00±10.51)%and 0.98±0.16 in the control group;the higher the concentration of ART,the lower the cell proliferation rate and Ki-67 protein expression;the differences were statistically significant(P<0.05).After different concentrations of ART were applied to HepG2 cells,the apoptosis rates of 30μg/mL group,60μg/mL group,and 120μg/mL group were(24.84±4.91)%,(36.02±7.35)%,and(50.27±10.02)%,respectively,and the expression levels of Bax protein were 0.26±0.05,0.39±0.06,0.58±0.08,Bcl-2 protein were 0.62±0.07,0.48±0.06,and 0.33±0.04,and Caspase-3 protein were 10.26±0.68,12.47±0.77,and 14.96±0.81,respectively,versus(5.75±1.63)%,0.17±0.03,0.83±0.09,and 8.73±0.46 in the control group;compared with the control group,the apoptosis rates,Bax,and Caspase-3 protein expression in 30μg/mL group,60μg/mL group,and 120μg/mL group were significantly increased,while Bcl-2 expression was significantly decreased;the higher the concentration of ART,the higher the apopt

关 键 词：青蒿琥酯 磷脂酞肌醇3-激酶/蛋白激酶B通路 肝癌细胞 细胞增殖 细胞迁移 

分 类 号：R735.7[医药卫生—肿瘤]