Effects of Cholesterol-lowering Agents on Proliferation, Invasion and Neutrophil Extracellular Trap Formation in Liver Cancer Cells
10.3971/j.issn.1000-8578.2022.22.0280
- VernacularTitle: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
- Author:
Qiqi TANG
1
;
Yan LI
;
Guowei SUN
;
Beibei LIANG
;
Jian ZHAO
Author Information
1. Graduate School, Shanghai University of Traditional Medicine, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
Liver cancer;
Cholesterol biosynthesis;
Proliferation;
Invasion;
Stemness character;
Neutrophil extracellular traps
- From:
Cancer Research on Prevention and Treatment
2022;49(11):1119-1125
- CountryChina
- Language:Chinese
-
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.
