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Many studies have demonstrated the function of nitric oxide (NO) or nitricoxide synthase-2 (NOS-2) in cancer as pro-neoplastic or anti-neoplastic effectors,but the role of NO and NOS-2 in hepatocellular carcinoma (HCC) remains unclear.The aim of this study was to investigate the levels of NO production and NOS-2expression in HCC and adjacent non-tumor liver tissues and to clarify whetherthe levels of NO/NOS-2 are related to the clinicopathological features of HCC.The levels of NO production were examined in tumor and adjacent non-tumor livertissues of 30 patients with HCC. The expression of NOS-2 was detected by real-timepolymerase chain reaction (RT-PCR) and immunohistochemical analysis in HCC and/oradjacent non-tumor liver tissues. Mutant p53 and proliferating cell nuclear antigen(PCNA) were also immunohistochemically investigated in liver tissues. The levelsof NO in HCC were significantly lower compared to adjacent non-tumor liver tissues(P&lt;0.001). The relative mRNA and protein expression levels of NOS-2 in HCCwere also significantly lower compared to adjacent non-tumor liver tissues (P&lt;0.01for both). We found that the levels of NO in patients suffering from HCC metastasiswere lower compared to those without metastasis (P&lt;0.05) and NOS-2 expressionwas correlated with tumor diameter (P&lt;0.05) and metastasis (P&lt;0.05). Inaddition, mutant p53 protein was expressed in the majority of HCC samples andthe proliferation rate of HCC was significantly higher than that of adjacent non-tumorliver tissues. These data indicate that decreased levels of NO/NOS-2 may partiallycontribute to overexpression of the mutant p53 protein and excessive proliferation;this may be a potential mechanism in the development and progression of HCC.

molecular medicine reports

Decreased levels of nitric oxide production and nitric oxide synthase-2 expression are associated with the development and metastasis of hepatocellular carcinoma