Sorafenib inhibition of hepatic stellate cell activation in the microenvironment of hepatocellular carcinoma
10.3760/cma.j.issn.1007-8118.2013.12.013
- VernacularTitle:索拉菲尼抑制肝星状细胞活化在肝癌肿瘤微环境中的作用机制
- Author:
Zhimin GENG
;
Bo LI
;
Lin WANG
;
Chen CHEN
;
Wenzhi LI
;
Jianbao ZHENG
- Publication Type:Journal Article
- Keywords:
Sorafenib;
Hepatocellular carcinoma;
Hepatic stellate cells;
Tumor microenvironment
- From:
Chinese Journal of Hepatobiliary Surgery
2013;19(12):925-929
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects and mechanisms of sorafenib on hepatic stellate cell viability and activation in the microenvironment of liver tumor.Methods The effects of LX2 cells on HepG2 cell proliferation were observed by coculture of LX2 and HepG2 cells.MTT assay was used to observe the effects of sorafenib on LX2 proliferation,and expression of α-smooth muscle actin (α-SMA) was measured immunocytochemically in LX2 cells treated with different concentrations of sorafenib.Changes in PDGF-BB and TGF-β1 concentrations were detected in LX2 supernatant using ELISA.Expression of ERK1,ERK2,and AKT signaling pathways were measured using Western blot.Furthermore,LX2 cells were cocultured with HepG2 cells for 24 hours to observe their effects on the invasive ability of HepG2 cells.Result After coculture of LX2 and HepG2 cells,HepG2 cells increased in the experimental group more than those of in the control group.After treatment with various concentrations of sorafenib for 12,24,36 or 48 hours,the viability of treated LX2 cells was lower than the controls in a concentration-and time-dependent manner.As sorafenib concentration and time of exposure increased,α-SMA expression became weaker in treated cells.PDGF-BB and TGF-β1 concentrations decreased with higher sorafenib concentrations and with longer exposure under the same concentration.ERK1,ERK2 and Akt expression was identical between treated and control groups,but their phosphorylated expression decreased with increased concentrations of sorafenib.The invasive ability of HepG2 cells induced by LX2 gradually decreased as sorafenib concentrations increased.Conclusions Sorafenib suppressed α-SMA expression,inhibited PDGF-dependent signaling pathways in HSCs,downregulated PDGF-BB and TGF β1 expression in the supernatant of HSCs,and restrained the viability and activation of HSCs.Sorafenib treatment therefore resulted in suppressed proliferation and invasion of HepG2 cells.
