摘要：Hepatocellular carcinoma (HCC) is the most common disorder of liver tumor which often leads to death. Indeed the incidence of HCC has been increased worldwide particularly in developing countries. The serious risk factors associated with HCC development are hepatitis C and B virus infection. Other considered risk factors include alcohol consumption, exposure to environmental toxins such as aflatoxins, hemochromatosis, cirrhosis, diabetes and obesity. A variety of cellular signaling pathways are implicated in HCC such as vascular endothelial growth factor signaling (VEGF), fibroblast growth factor signaling (FGF) and mitogen-activated protein kinase (MAPK). Thus, in the current study we were interested to investigate one of MAPK signals, RAF/MEK/ERK pathway in HCC using HepG2 cells compared with normal hepatocytes cells. The relative gene expression of MAPK and production level of tumor necrosis factor alpha (TNF-α) during cells growth have been `assessed using quantitative real time PCR and quantitative 'sandwich' ELISA assay, respectively. Our results indicate that the growth of HepG2 cells require time-dependent RAF/MEK signaling pathway; the relative expression of RAF and MEK genes are positively associated with cell growth. Further, the production level of TNF-α was increased during HepG2 cells growth in comparison with normal cells. Interestingly, both RAF/MEK pathway and production level of TNF-α are sufficiently regulated in HepG2 cells that were subjected to Raf-1 inhibitor. These data firstly reveal the important clue for exploiting the relative gene expression of RAF/MEK and production level of TNF-α in diagnosis of HCC development. Secondary, our findings provide the potential anti-cancer effect of Raf-1 inhibitor via regulation of RAF/MEK signaling and prevent TNF-α production.
关键词：Hepatocellular carcinoma; RAF/MEK pathway; TNF-α; Diagnosis and therapy
