熊果酸联合HDAC2抑制剂抑制人肝癌细胞系HepG2的增殖

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (8): 1144-1150.

熊果酸联合HDAC2抑制剂抑制人肝癌细胞系HepG2的增殖

唐加峰¹, 何雪莲², 夏菁¹, 熊伟¹, 李小山^1*

1.重庆三峡医药高等专科学校,重庆 404120;
2.重庆大学附属三峡中心医院,重庆 404100

收稿日期:2021-01-07 修回日期:2021-06-03 出版日期:2021-08-05 发布日期:2021-07-21
通讯作者: *43789764@qq.com
基金资助:
重庆市卫生健康委员会中医项目(zy201602100);重庆市教育委员会科技项目(KJ1725389);重庆三峡医药高等专科学校重大项目(2016xzzd06)

Ursolic acid combined with HDAC2 inhibitor inhibits proliferation of human hepatoma cell line HepG2

TANG Jia-feng¹, HE Xue-lian², XIA Jing¹, XIONG Wei¹, LI Xiao-shan^1*

1. Chongqing Three Gorges Medical College, Chongqing 404120;
2. Three Gorges Central Hospital Affiliated to Chongqing University, Chongqing 404100, China

Received:2021-01-07 Revised:2021-06-03 Online:2021-08-05 Published:2021-07-21
Contact: *43789764@qq.com

摘要/Abstract

摘要： 目的探讨熊果酸(UA)联合HDAC2抑制剂(SA)对人肝癌细胞HepG2增殖的影响及潜在作用机制。方法通过 CCK-8法、光学显微镜观察、细胞克隆形成实验及流式细胞术检测UA和SA单用和联合作用于HepG2细胞后对细胞增殖的抑制作用,Western blot检测细胞内HDAC2、AC-α-tubulin、CDK2、CDK1、Bax、Bcl-2和cleaved-PARP的表达。结果 UA对HepG2细胞的增殖有明显的抑制作用,呈浓度和时间依赖性(P＜0.01);UA可以抑制HepG2细胞克隆形成能力,联合SA后抑制作用更为显著(P＜0.01);UA联合SA可使HepG2细胞周期阻滞于G₁期(P＜0.01);HDAC2在肝癌细胞系SMMC-7721、HepG2和PLC5中高表达,UA联合SA可以明显下调HepG2细胞中HDAC2、Bcl-2、CDK2和cyclin E1蛋白的表达水平,同时上调AC-α-tubulin、Bax和cleaved-PARP蛋白表达水平。结论 UA联合SA应用对HepG2细胞的增殖具有协同抑制作用。

关键词: 熊果酸, 肝癌, 组蛋白去乙酰化酶2(HDAC2), 增殖

Abstract: Objective To investigate the effect of ursolic acid (UA) combined with HDAC2 inhibitor (SA) on the growth and proliferation of human hepatocarcinoma cell line HepG2 and its potential mechanism. Methods CCK-8, optical microscopy, cell clone formation and flow cytometry were used to evaluate the inhibitory effects of UA and SA on HepG2 cells after UA and SA monotherapy or combination therapy. Western blot was used to analyze the expression of HDAC2, AC-α-tubulin CDK2, CDK1, Bax, Bcl-2, and cleaved-PARP in the HepG2 cells after the treatment. Results UA had a significant inhibitory effect on the growth of HepG2 with a concentration and time-dependent manner (P＜0.01); UA inhibited HepG2 cell cloning, and the inhibitory effect was more significant when combined with SA (P＜0.01). UA combined with SA blocked HepG2 cell cycle at G₁ phase (P＜0.01); HDAC2 was highly expressed in human hepatoma SMMC-7721, HepG2, and PLC5 cell lines, and UA combined with SA significantly down-regulated HDAC2, Bcl-2, CDK2 and cyclin E1 protein expression, while up-regulated the expression of AC-α-tubulin, Bax and cleaved-PARP. Conclusions The combined application of UA and SA has a synergistic inhibitory effect on the proliferation of HepG2 cells.

Key words: ursolic acid, liver cancer, histone deacetylase 2 (HDAC2), proliferation

中图分类号:

R735.2

唐加峰, 何雪莲, 夏菁, 熊伟, 李小山. 熊果酸联合HDAC2抑制剂抑制人肝癌细胞系HepG2的增殖[J]. 基础医学与临床, 2021, 41(8): 1144-1150.

TANG Jia-feng, HE Xue-lian, XIA Jing, XIONG Wei, LI Xiao-shan. Ursolic acid combined with HDAC2 inhibitor inhibits proliferation of human hepatoma cell line HepG2[J]. Basic & Clinical Medicine, 2021, 41(8): 1144-1150.

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