临床肝胆病杂志2025,Vol.41Issue(4):690-697,8.DOI:10.12449/JCH250414
同源盒基因A6(HOXA6)调控肝癌HepG2细胞增殖、侵袭、转移和凋亡的作用机制
Mechanism of action of Homebox A6 in regulating the proliferation,invasion,metastasis,and apoptosis of HepG2 hepatoma cells
摘要
Abstract
Objective To investigate the effect of Homebox A6(HOXA6)on the proliferation,invasion,metastasis,and apoptosis of HepG2 hepatoma cells and its association with the PI3K/AKT signaling pathway.Methods HepG2 hepatoma cells were cultured,and HOXA6 overexpression plasmid and siRNA were constructed and transfected into cells.The cells were randomly divided into empty plasmid group,HOXA 6 overexpression group,siRNA negative control group,and siRNA HOXA6 interference group.CCK8 assay was used to measure cell proliferation,Transwell assay was used to observe cell invasion,and wound healing assay was used to observe cell migration(related proteins TIMP3,MMP9,and MMP3).Flow cytometry was used to measure cell apoptosis(related proteins BAX and BCL2),the BCA method was used to measure protein concentration,and Western Blot was used to measure the expression of related proteins.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the SNK-q test was used for further comparison between two groups.Results Compared with the empty plasmid group,HOXA6 overexpression significantly promoted the proliferation,invasion,and migration of HepG2 hepatoma cells(all P<0.001),and there was a significant reduction in the protein expression of TIMP3(P<0.001),while there were significant increases in the expression levels of MMP9 and MMP3(both P<0.001).Compared with the siRNA negative control group,HOXA6 interference significantly inhibited the proliferation,invasion,and migration of HepG2 hepatoma cells(all P<0.001),and there was a significant increase in the protein expression of TIMP3(P<0.001),while there were significant reductions in the expression levels of MMP9 and MMP3(both P<0.001).Flow cytometry showed that compared with the empty plasmid group,HOXA6 overexpression inhibited the apoptosis of HepG2 hepatoma cells(P<0.001),with a significant reduction in the expression of the apoptosis-related protein BAX and a significant increase in the expression of BCL2(both P<0.001).Compared with siRNA negative control group,HOXA6 interference promoted the apoptosis of HepG2 hepatoma cells(P<0.001),with a significant increase in the expression of BAX and a significant reduction in the expression of BCL2(both P<0.001).Compared with the empty plasmid group,the HOXA6 overexpression group had significantly higher ratios of p-AKT/AKT and p-PI3K/PI3K(both P<0.001),and compared with the siRNA negative control group,the siRNA HOXA6 interference group had significantly lower ratios of p-AKT/AKT and p-PI3K/PI3K(both P<0.001).Conclusion HOXA6 can promote the proliferation,invasion,and metastasis of HepG2 hepatoma cells and inhibit their apoptosis by activating the PI3K/AKT signaling pathway through phosphorylation.关键词
Hep G2细胞/基因,同源盒/细胞增殖/细胞凋亡Key words
Hep G2 Cells/Genes,Homeobox/Cell Proliferation/Apoptosis引用本文复制引用
刘玉婷,麦静愔,侯天禄,成扬..同源盒基因A6(HOXA6)调控肝癌HepG2细胞增殖、侵袭、转移和凋亡的作用机制[J].临床肝胆病杂志,2025,41(4):690-697,8.基金项目
国家自然科学基金面上项目(82374189,81774098) General Projects of the National Natural Science Foundation of China(82374189,81774098) (82374189,81774098)