实用医学杂志2025,Vol.41Issue(10):1480-1486,7.DOI:10.3969/j.issn.1006-5725.2025.10.008
三白草酮调控Krüppel样因子5-促红细胞生成素肝细胞A2通路对肝癌细胞生长和免疫逃逸的影响
Effects of sauchinone regulating KLF5-EphA2 pathway on the growth and immune escape of hepatocellular carcinoma cells
摘要
Abstract
Objective To investigate the effects of sauchinone(Sch)on the growth and immune escape of liver cancer cells by regulating the Krüppel like factor 5(KLF5)-erythropoietin-producing hepatocellular receptor A2(EphA2)pathway.Methods Huh-7 cells were grouped into liver cancer group,Sch low,medium,and high-dose groups(Sch-L group,Sch-M group,Sch-H group),Sch-H+KLF5 activator negative control group(OE-NC),and Sch-H+KLF5 activator(OE-KLF5)group.5-bromo-2-deoxyuracil(EdU)staining,CCK-8,scratch assay,and Transwll were used to detect the proliferation,migration,and invasion of Huh-7 cells,respectively.Western blot was applied to detect proliferative cell nuclear antigen(PCNA),migration invasion enhancer(MIEN1),matrix metalloproteinase-2(MMP-2),programmed death receptor ligand 1(PD-L1),KLF5,and EphA2 proteins in Huh-7 cells.The Huh-7 cells in above 6 groups were co cultured with activated CD8+T cells in a 96 well plate and named as liver cancer co culture group,Sch-L co culture group,Sch-M co culture group,Sch-H co culture group,Sch-H+OE-NC co culture group,and Sch-H+OE-KLF5 co culture group.The killing rate of CD8+T cells in the co culture system and the levels of interferon-γ(IFN-γ),interleukin-4(IL-4),and tumor necrosis factor-α(TNF-α)in the supernatant were detected.Results Compared with the liver cancer group,the EdU positive rate,OD450 value,cell invasion number,and PCNA,MIEN1,MMP-2,PD-L1,KLF5,and EphA2 proteins in the Sch-L,Sch-M,and Sch-H groups reduced,the migration distance shorten(P<0.05).Compared with the Sch-H group and Sch-H+OE-NC group,the EdU positive rate,OD450 value,cell invasion number,and PCNA,MIEN1,MMP-2,PD-L1,KLF5,and EphA2 proteins in the Sch-H+OE-KLF5 group increased,the migration distance prolonged(P<0.05).Compared with the liver cancer co culture group,the killing rate of CD8+T cells on Huh-7 cells and the levels of IFN-γ,TNF-α,and IL-4 in the supernatant in the Sch-L co culture group,Sch-M co culture group,and Sch-H co culture group increased(P<0.05).Compared with the Sch-H co culture group and the Sch-H+OE-NC co culture group,the killing rate of CD8+T cells on Huh-7 cells and the levels of IFN-γ,TNF-α,and IL-4 in the supernatant in the Sch-H+OE-KLF5 co culture group decreased(P<0.05).Conclusion Sch may inhibit growth and immune escape of liver cancer cells by inhibiting the KLF5-EphA2 pathway.关键词
三白草酮/肝癌/免疫逃逸/Krüppel样因子5-促红细胞生成素肝细胞A2通路Key words
sauchinone/liver cancer/immune escape/krüppel like factor 5-erythropoietin-producing hepatocellular receptor A2 pathway分类
医药卫生引用本文复制引用
王山,万金良,赵中华,杨静,赵杰,郝延璋..三白草酮调控Krüppel样因子5-促红细胞生成素肝细胞A2通路对肝癌细胞生长和免疫逃逸的影响[J].实用医学杂志,2025,41(10):1480-1486,7.基金项目
山东省医学会临床科研项目(编号:YXH2022ZX02124) (编号:YXH2022ZX02124)