Inhibition Effects Of Biological Response Modifier On Hepatocellular Carcinoma In Vitro And In Vivo

To investigate molecular characters of BEL-7402 , it were studied under cDNA microarray. Then to observe the effects of Somatostatin with Interferon-alpha inhibited proliferation of BEL-7402 hepatocellular carcinoma(HCC) cell line and growth of HCC xenografts in nude mice. Finally , to evaluate security of administration of Somatostatin in HCC patients after resection of liver. We compared gene expression alteration between BEL-7402 cell line and normal liver tissue by cDNA microarray. Among 866 cancer related genes, there were 71 genes had differential expression in BEL-7402 cell line. 24 genes were up-regulated while 7 genes were down-regulated. In those genes, many differentially expressed genes were involved in cell division, membrane receptor and immunocompeten. Abnormal gene expression contribute to malignant cell divison. Cell survive rates and activities were detected by typan blue exclusion respectively, phase contrast microscopy , flowcytometer and cDNA microarray were used to detect the ability to inhibit the growth of BEL-7402 in vitro. It may be an important mechanism for Somatostatin inhibition of proliferative ability of BEL-7402 cells by inducing cell differentiation and modulating the cell cycle progress, rather than by killing the hepatocellular carcinoma cell or inducing apoptosis directly. Nude mice bearing xenografts of cancer cell line were treated with Somatostatin, Somatostatin and Interferon-alpha or saline control for 4 weeks after tumor implantation .The mechanism of Inhibition of Somatostatin on proliferative ability of tumor cells was observed bymeasuring tumor volume, MVD were detected with immunohistochemistry in three groups. Cell cycle progress and apoptosis were detected by flowcytometer, gene expression profile was identified by cDNA microarrays. The ratio of cell in resting state (G0/G1) increased, MVD decreasing , apopotosis peak was observed, there were 23 genes had differential expression. 7 genes were up-regulated while 16 genes were down-regulated, specific genes involved in modulating the cell cycle progress , apoptosis cascade. These finding suggest that the inhibition on effects occur in the growth of HCC transplant tumor in nude mice were markedly improved by Somatostatin combined with Interferon-alpha when compared with Somatostatin alone. To administrate Somatostatin was security after resection of liever, it could enhance wound healing. These synergic results may be of potential therapeutic benefit to those patients with HCC.