Inducible nitric oxide synthase expression is related to angiogenesis, bcl-2 and cell proliferation in hepatocellular carcinoma

ＩＮＴＲＯＤＵＣＴＩＯＮＮｉｔｒｉｃｏｘｉｄｅ (ＮＯ) ,ａｓｈｏｒｔｈａｌｆ ｌｉｆｅｒａｄｉｃａｌ,ｉｓｈｉｇｈｌｙｒｅａｃｔｉｖｅ ,ａｎｄｉｓｉｎｖｏｌｖｅｄｉｎｍａｎｙｂｉｏ ｌｏｇｉｃａｌｐｒｏｃｅｓｓｅｓ,Ｉｔｓｅｅｍｓｔｏｐｌａｙａｎｉｍｐｏｒｔａ

Inducible nitric oxide synthase expression is related to angiogenesis, bcl-2 and cell proliferation in hepatocellular carcinoma

In this study, we examined the expression of inducible nitric oxide s ynthase (iNOS) and vascular endothelial growth factor (VEGF) by immunohistoc hemi cal staining in 76 tissue sections collected from hepatocellular carcinoma (HCC) patients undergoing hepatectomy. Microvascular density (MVD) was determined by counting endothelial cells immunostained using anti-CD34 antibody. We performe d DNA-flow cytometric analyses to elucidate the impact of iNOS and VEGF expressi o n on the cell cycle of HCC. Most of the HCC cells that invaded stroma were mark edly immunostained by iNOS antibody. The iNOS stain intensity of the liver tissu e close to the tumor edge was stronger than that of HCC tissue, and the stronges t was the hepatocytes closer to the tumor tissue. However, iNOS expression in 10 normal hepatic samples was undetectable. VEGF positive expression ratio was 84. 8% in iNOS positive expression cases, and the ratio was 35.3% in negative cases. There was significant correlation (P=0.000) between iNOS and VEGF expressi on. Moreover, iNOS expression was significantly associated with bcl-2 and MVD, but w ithout p53 expression. DNA-flow cytometric analyses showed that combined expres s ion of iNOS and VEGF had significant impact on the cell cycle in HCC. PI (Proli ferating Index) and SPF (S-phase fraction) in the combined positive expression o f iNOS and VEGF group was significantly higher than that in the combined negativ e group. The present findings suggested that iNOS expression was significantly a ssociated with angiogenesis, bcl-2 and cell proliferation of HCC.