摘要
目的:探究组蛋白去乙酰化酶抑制剂LBH589联合阿帕替尼对人肝癌细胞HepG2的抑制作用。方法:分别使用不同浓度组蛋白去乙酰化酶抑制剂LBH589、阿帕替尼单药及两药联合处理人肝癌细胞HepG2细胞系24 h、48 h、72 h后,采用CCK-8法检测吸光度计算增殖抑制率;采用Western印迹法检测表皮生长因子受体(EGFR)信号通路表达情况。结果:LBH589组、阿帕替尼组和联合组HepG2细胞增殖抑制作用均呈时间和浓度依赖性,随处理药物浓度增加及作用时间延长,抑制作用逐渐增强,且联合组抑制作用更高。联合组对HepG2细胞增殖的抑制作用较LBH589组和阿帕替尼组明显增强。Western印迹检测结果显示,经LBH589、阿帕替尼单独或联合处理后的HepG2细胞磷酸化(p)-EGFR、p-细胞外调节蛋白激酶(ERK1/2)和p-蛋白激酶B(AKT)表达较空白对照组均有不同程度下调,且联合组抑制作用最强。结论:组蛋白去乙酰化酶抑制剂LBH589、阿帕替尼单药及其联合对人肝癌细胞HepG2均有一定抑制作用,随处理药物浓度增加及作用时间延长,抑制作用逐渐增强,且二者联合时的抑制作用更强,可有效抑制EGFR信号通路表达。
Objective To investigate the inhibitory effect of histone deacetylase inhibitor LBH589 combined with Apatinib on human hepatoma cells HepG2.Methods HepG2 cell lines were treated with histone deacetylase inhibitor LBH589,Apatinib single drug,or the combination of two drugs at different concentrations for 24 h,48 h,and 72 h,respectively,and the absorbance was detected by the CCK-8 method to calculate the proliferation inhibition rate.The expression of the EGFR signaling pathway was detected by Western Blot.Results The inhibition of HepG2 cell proliferation in the LBH589 group,Apatinib group,and combination group was time-and dose-dependent.With the increase of treatment concentration and prolongation of treatment time,the inhibitory effect was gradually enhanced,and the inhibitory effect was higher in the combination group.Compared with the LBH589 group and Apatinib group,the inhibitory effect of the combination group on HepG2 cell proliferation was significantly enhanced.Western blot results showed that the expressions of p-EGFR,p-ERK1/2,and p-AKT in HepG2 cells treated with LBH589 and Apatinib alone or in combination were down-regulated to varying degrees compared with the blank control group,and the combination group had the strongest inhibitory effect.Conclusions Histone deacetylase inhibitor LBH589,Apatinib single drug,and their combination have certain inhibitory effects on the human hepatoma cell line HepG2.With the increase of treatment drug concentration and prolongation of action time,the inhibitory effect is gradually enhanced,and the combination of the two drugs has a stronger inhibitory effect,which can effectively inhibit the expression of the EGFR signaling pathway.
作者
杨志刚
章燕燕
周育宏
YANG Zhi-Gang;ZHANG Yan-Yan;ZHOU Yu-Hong(The First Department of Surgery,Armed Police Jiangxi General Hospital,Nanchang 330006,Jiangxi,China)
出处
《吉林医学》
2025年第8期1793-1796,共4页
Jilin Medical Journal
基金
江西省卫健委科技计划[项目编号:SKJP220234595]。
