降脂药对肝癌细胞增殖、侵袭及中性粒细胞外诱捕网形成的影响  

Effects of Cholesterol-lowering Agents on Proliferation, Invasion and Neutrophil Extracellular Trap Formation in Liver Cancer Cells

作　　者：汤琦琦 李艳 孙国伟 梁蓓蓓[2] 赵健 TANG Qiqi;LI Yan;SUN Guowei;LIANG Beibei;ZHAO Jian(Graduate School,Shanghai University of Traditional Medicine,Shanghai 201203,China;Shanghai Key Laboratory of Molecular Imaging,Shanghai University of Medicine and Health Sciences,Shanghai 201318,China;Out-patient Department,Beijing Garrison District 29th Retired Cadres Rest Home,Beijing 100191,China)

机构地区：[1]上海中医药大学研究生院,上海201203 [2]上海健康医学院上海市分子影像重点实验室,上海201318 [3]北京卫戍区第29离职干部休养所门诊部,北京100191

出　　处：《肿瘤防治研究》2022年第11期1119-1125,共7页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金面上项目(81972252,81670573)。

摘　　要：目的探讨降脂药对肝癌细胞增殖、干性特征、迁移、侵袭和中性粒细胞外诱捕网(NETs)形成的作用。方法下调ASPP2或HMGCR基因建立胆固醇合成增加或减弱的小鼠肝癌细胞Hepa1-6,分别用辛伐他汀和黄连素两种降脂药处理。CCK-8和平板克隆实验检测肝癌细胞增殖能力;低吸附板成球和qRT-PCR分析细胞干性特征和相关基因表达;划痕和Transwell实验分析细胞迁移、侵袭能力。免疫荧光染色分析NETs形成。结果降脂药可显著抑制Hepa1-6细胞贴壁和成球生长及干性基因表达(P<0.001);显著抑制Hepa1-6细胞迁移和侵袭能力(P<0.001);显著抑制中性粒细胞诱导的Hepa1-6细胞侵袭和NETs的生成(P<0.001)。结论降脂药通过抑制肝癌细胞的干性特征和NETs形成,抑制肝癌细胞增殖和转移,是治疗肝癌转移的一种潜在方式。Objective To investigate the effects of cholesterol-lowering agents on the proliferation,stemness characters,migration,invasion,and neutrophil extracellular traps formation(NETs)formation in liver cancer cells.Methods ASPP2 or HMGCR gene was knocked down in mouse liver cancer cell Hepa1-6 to establish cells with high or low cholesterol,respectively.Simvastatin and berberine were used to reduce cholesterol synthesis.CCK-8 and plate cloning assays were conducted to detect the proliferation ability of liver cancer cells.Sphere formation assay and qRT-PCR were used to analyze the stemness character and expression of related genes.Wound-healing assay and Transwell assay were used to analyze the ability of cell migration and invasion.Immunofluorescence staining was carried out to analyze the effect of lipid-lowering agent on NETs formation.Results Cholesterol-lowering agents significantly inhibited the proliferation and stemness-related gene expression of Hepa1-6 cells(P<0.001),significantly inhibited the migration and invasion of Hepa1-6 cells(P<0.001),and significantly inhibited the neutrophil-induced invasion and formation of NETs(P<0.001).Conclusion Cholesterol-lowering agents suppress the proliferation and invasion via inhibiting the stemness characters and NETs formation in liver cancer cells.It is a potential strategy for the treatment of liver cancer metastasis.

关 键 词：肝癌 胆固醇合成 增殖 侵袭 干性特征 中性粒细胞外诱捕网 

分 类 号：R735.7[医药卫生—肿瘤]