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汤琦琦, 李艳, 孙国伟, 梁蓓蓓, 赵健. 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[J]. 肿瘤防治研究, 2022, 49(11): 1119-1125. DOI: 10.3971/j.issn.1000-8578.2022.22.0280
引用本文: 汤琦琦, 李艳, 孙国伟, 梁蓓蓓, 赵健. 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[J]. 肿瘤防治研究, 2022, 49(11): 1119-1125. DOI: 10.3971/j.issn.1000-8578.2022.22.0280
TANG Qiqi, LI Yan, SUN Guowei, LIANG Beibei, ZHAO Jian. Effects of Cholesterol-lowering Agents on Proliferation, Invasion and Neutrophil Extracellular Trap Formation in Liver Cancer Cells[J]. Cancer Research on Prevention and Treatment, 2022, 49(11): 1119-1125. DOI: 10.3971/j.issn.1000-8578.2022.22.0280
Citation: TANG Qiqi, LI Yan, SUN Guowei, LIANG Beibei, ZHAO Jian. Effects of Cholesterol-lowering Agents on Proliferation, Invasion and Neutrophil Extracellular Trap Formation in Liver Cancer Cells[J]. Cancer Research on Prevention and Treatment, 2022, 49(11): 1119-1125. DOI: 10.3971/j.issn.1000-8578.2022.22.0280

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

  • 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。

     

    Abstract:
    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.

     

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