Hepatic Stellate Cells Induce Proliferation And Emt Via ERK1/2 Signaling Pathway In Human Hepatoma Cells

Objective To investigate the influence of hepatic stellate cells(HSC)on malignant biological behavior of hepatoma cells and related mechanisms.Methods Human hepatoma cells line SMMC-7721 and HepG2 and hepatic stellate cells line LX-2 were cultured respectively and treated with LX2-CM and specific inhibitors(U0126)of extracellular regulated protein kinases(ERK1/2).The migration and invasion ability of human hepatoma cells were detected by transwellTM assay.The cell proliferation was analyzed by CCK-8 assay.Western blot and qRT-PCR were used to determined the protein level of phosphorylated of ERK1/2,and the mRNA and protein expressions of ERK1/2,c-Myc oncogenes(c-Myc),vimentin(vimentin),E-cadherin(E-cadherin).Results TranswellTM test and CCK-8 assay demonstrated that LX2-CM can promote the proliferation,invasion and migration of SMMC-7721 and HepG2 cells,U0126 can inhibit the effect in human hepatoma cells.LX2-CM up-regulated the expression of p-ERK1/2,c-Myc,Vimentin and down-regulated the expression of E-cadherin.Besides,U0126 treatment significantly decreased the protein and mRNA expression of p-ERK1/2,c-Myc,vimentin,while those of E-cadherin were enhanced.Conclusion LX2-CM could activate c-Myc via ERK1/2 signaling pathway in hepatoma cells,and consequently promote cell proliferation,invasion and migration,and also induce epithelial mesenchymal transformation.