ABSTRACT
OBJECTIVE: To assess the role of HO-1 in HCC progression and to study the expression of apoptotic factors represented by TNF-alpha, and Fas-L versus antiapoptotic and angiogenic factors represented by HO-1, TGF-beta, HGF, and VEGF in HCC compared to non cancerous cirrhotic liver. DESIGN AND METHODS: Liver biopsies were taken from twelve patients with grade II HCC confined to the liver and twelve patients with non cancerous liver cirrhosis (served as control). RT-PCR of previous genes was evaluated. RESULTS: HO-1, VEGF, HGF, and TNF-alpha genes were significantly increased (P<0.05) in HCC compared to control. Fas-L showed a significant decrease (P<0.05) in HCC compared to control. TGF-beta was higher in HCC than control but the difference was not statistically significant (P>0.05). HGF showed significant positive correlation with HO-1 (r=0.8217, P=0.001). CONCLUSION: HCC is associated with increased expression of VEGF, HGF, and TGF-beta, and with suppression of Fas-L. In addition, HO-1 is highly significantly expressed in HCC. The significant positive correlation between HO-1 and HGF was first reported in Egyptian human liver biopsies, and this suggests that it may play a role in the progression of hepatocellular carcinoma.
Subject(s)
Angiogenic Proteins/biosynthesis , Apoptosis Regulatory Proteins/biosynthesis , Carcinoma, Hepatocellular/metabolism , Heme Oxygenase-1/biosynthesis , Liver Neoplasms/metabolism , Adult , Angiogenic Proteins/genetics , Apoptosis Regulatory Proteins/genetics , Biopsy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cytokines/genetics , Electrophoresis, Agar Gel , Humans , Liver Cirrhosis/genetics , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Middle Aged , RNA/genetics , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
The present study was conducted to investigate if the mechanism of human heme oxygenase-1 (HO-1) mediated angiogenesis was through the induction of vascular endothelial growth factor (VEGF). Also, the effect of HO-1 on the expression of transforming growth factor beta (TGF-beta),was studied in the presence and absence of HO-1 inducers. Rat lung microvessel endothelial cell line transduced with human HO-1 gene was subjected to cell culture (six separate experiments). mRNA extraction and reverse transcriptase polymerase chain reaction (RT-PCR) experiments, were performed to evaluate the expression of HO-1, VEGF, and TGF-beta in the presence and absence of HO inducers including H(2)O(2), endotoxin and snake venom metalloproteinase with disintegrin like activity(SnMP). ELISA technique was performed to evaluate the levels of the studied growth factors. The results of the study showed over expression of VEGF in endothelial cells transduced with HO-1 compared to control non-transduced endothelial cells. On the other hand, the expression of TGF-beta and its protein level were markedly inhibited in HO-1 transduced endothelial cells compared to control non-transduced cells. Endotoxin and SnMP showed more prominent effect on the expression of VEGF and suppression of TGF-beta in HO-1 transduced endothelial cells, suggesting that their effect is most probably mediated through induction of HO-1.
