双氢青蒿素通过抑制HMGB2表达及逆转EMT进程抑制肝癌细胞生长及侵袭  

Dihydroartemisinin inhibits growth and invasion of hepatoma cells by inhibiting expression of HMGB2 and reversing process of EMT

作　　者：杨晨雪 魏雁虹[2] 魏海峰[3] 米旭光 宋帅[2] 李明[2] 耿辉[2] 杨广民(指导)[2] YANG Chenxue;WEI Yanhong;WEI Haifeng;MI Xuguang;SONG Shuai;LI Ming;GENG Hui;YANG Guangmin(Changchun University of Chinese Medicine,Changchun 130021,China)

机构地区：[1]长春中医药大学,长春130021 [2]吉林省人民医院医学检验中心,长春130021 [3]吉林省人民医院肿瘤生物治疗与基因诊断重点实验室,长春130021

出　　处：《中国免疫学杂志》2022年第5期557-562,共6页Chinese Journal of Immunology

基　　金：吉林省科技厅自然科学基金项目(20200201346JC);吉林省卫生计生青年科研课题(2015Q046)资助。

摘　　要：目的:观察双氢青蒿素(DHA)对体外生长的肝癌细胞生物学行为的影响,并探讨其作用机制。方法:体外培养人肝癌细胞HepG2和LM3,采用不同浓度DHA处理,设立不加药的阴性对照组并以顺铂作为阳性对照。MTT、流式细胞术分别检测DHA对肝癌细胞增殖及凋亡的影响;划痕实验、Transwell实验分别观察DHA对肝癌细胞迁移及侵袭能力的影响;Western blot检测DHA对肝癌细胞凋亡相关蛋白、HMGB2及EMT相关蛋白表达的影响。结果:与阴性对照组相比,DHA处理后的肝癌细胞存活率降低、凋亡率提高,迁移及侵袭能力降低(P<0.05),HMGB2蛋白表达显著降低,凋亡相关蛋白Cleavedcaspase3、Bax表达显著增加,Bcl-2表达显著减少,EMT相关蛋白E-cadherin表达显著增加,N-cadherin、Vimentin表达显著减少(P<0.05)。结论:DHA可抑制肝癌细胞生长,促进其凋亡,降低其迁移及侵袭能力,其机制可能为DHA通过降低HMGB2表达抑制肝癌细胞EMT进程。Objective:To observe effect of dihydroartemisinin(DHA)on biological behavior of hepatoma cells in vitro and to explore its mechanism.Methods:Human hepatoma cells HepG2 and LM3 were cultured in vitro and treated with different concentrations of DHA.Negative control group without dosing was established,and cisplatin was used as positive control.Effects of DHA on proliferation and apoptosis of hepatocellular carcinoma cells were examined by MTT and flow cytometry.Effects of DHA on migration and invasion of hepatocellular carcinoma cells were observed by scratch test and Transwell assays.Effects of DHA on expressions of apoptosis related proteins,HMGB2 and EMT related proteins in hepatoma cells were detected by Western blot.Results:Compared with negative control group,after DHA treatment,survival rate of hepatoma cells was decreased,apoptosis rate was increased,and migration and invasion ability were decreased(P<0.05),expression of HMGB2 protein was significantly decreased,expressions of apoptosis related proteins Cleaved-caspase3 and Bax were significantly increased,Bcl-2 expression was significantly decreased,expression of EMT related protein E-cadherin was significantly increased,expressions of N-cadherin and Vimentin were significantly decreased(P<0.05).Conclusion:DHA can inhibit growth of hepatocellular carcinoma cells,promote its apoptosis,and reduce its migration and invasion ability,whose mechanism may be DHA inhibits EMT process of hepatocellular carcinoma cells by decreasing expression of HMGB2.

关 键 词：双氢青蒿素 肝细胞癌 迁移 凋亡 高迁移率族蛋白B2 上皮-间质转化 

分 类 号：R735.7[医药卫生—肿瘤]