Expression Features Of Nuclear-transcription Factor- κB And Intervention Of Its Single Transduction Pathway On Influences Of Malignant Transformation Of Hepatocytes

Objective Hepatocellular carcinoma (HCC) is characterized by multi- cause and obvious multistage, multifocus process of tumor progression. Development of HCC is related intimately with over-expression and signal transduction of many cellular factors. The aim of this study was to investigate the dynamic expression of NF-κB during HCC development and the influences on malignant transformation of hepatocytes through the intervention of NF-κB activation pathway.Methods Rat hepatoma models were induced with 2-fluorenylacetamide (2-FAA, 0.05 %) on male Sprague-Dawly (SD) rats, thalidomide diluted with olive oil (1 g/40mL) was administered intragastrically (100 mg/kg body weight daily) to intervence the progress of hepatoma. A part of rats of each group were sacrificed fortnightly interval to the twelfth week. Morphological changes were observed by pathological examinations (HE staining). The NF-κB expressions in nucleus were detected by enzyme linked immunosorbent assay (ELISA). The NF-κB expressions in rat or human liver tissues were semi-quantitatively analyzed by immuno- histochemistry. The relationship between NF-κB expression and the clinical pathological characteristics in human HCC and their non-cancerous tissues were analyzed and its clinical values were explored in the present study. Results Histological examinations evidenced that hepatocytes in rats fed with 2-FAA showed vacuole-like denaturations at the early stages, then dysplastic nodules appeared at middle stage, and finally progressed to tubercles of cancerous nest, all of which were highly differentiated HCC. It was found that thalidomine can repress the morphologic change of liver cells. There were only punctiform denaturations at the early and middle stage; Nodosity hyperplasy and minority atypical hyperplasia were found at the finally stage. The results of immunohistochemistry demonstrated that the NF-κB level of liver tissues in hepatoma rats was significantly higher than those in normal ones (P<0.01) , and the NF-κB level of liver tissues in inducing hepatoma group was higher than those in thalidomide group (χ2=9.93,P<0.05). An increasing tendency of liver nucleus NF-κB protein was found from normal liver to precancerous to cancerous tissues during rat hepatoma development by ELISA (P<0.01). The levels of nucleus NF-κB in hepatoma rats were significantly higher than those in normal ones(t=6.83, P<0.01). The levels of NF-κB with thalidomide intervence raised first and decreased later. The expressions of NF-κB in human HCC tissues were higher (χ2=21.3, P<0.01) than that in their non-cancerous tissues. No positive relationship presented between NF-κB expression and histological differentiation grade or the number of tumor, size of tumor, and HBsAg positive.Conclusion The overexpression of hepatic NF-κB is observed during HCC development. Chemical intervence with thalidomide can decrease NF-κB expression, and inhibit the development of hepatoma, suggesting that NF-κB is expected to be a new molecular target of hepatoma gene therapy.