trichostatin-a and Bile-Duct-Neoplasms

To explore the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the growth of biliary tract cancer cell lines (gallbladder carcinoma cell line and cholangiocarcinoma cell line) in vivo and in vitro, and to investigate the perspective of histone deacetylase inhibitor in its clinical application.. The survival rates of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) treated with various doses of TSA were detected by methylthiazoy tetrazolium (MTT) assay. A nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-l cell line) was successfully established, and changes in the growth of transplanted tumor after treated with TSA were measured.. TSA could inhibit the proliferation of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) in a dose-dependent manner. After the nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-l cell line) was successfully established, the growth of cancer was inhibited in the model after treated with TSA.. TSA can inhibit the growth of cholangiocarcinoma and gallbladder carcinoma cell lines in vitro and in vivo.

Topics: Animals; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cell Division; Cell Line, Tumor; Cholangiocarcinoma; Enzyme Inhibitors; Gallbladder Neoplasms; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Survival Rate; Transplantation, Heterologous

We examined expression of maspin and the epigenetic status of its gene in 40 primary hepato-biliary tract carcinomas and 11 cell lines originating from hepato-pancreatico-biliary tract carcinomas. Aberrant maspin expression was frequently observed immunohistochemically in biliary tract carcinomas (22/25, 88%) but not in hepatocellular carcinomas (HCCs) (0/15, 0%). Aberrant maspin expression by five pancreatico-biliary tract carcinoma cell lines was closely associated with demethylation at the maspin promoter. Five of six HCC cell lines were maspin-negative and exhibited extensive hypomethylation and hypoacetylation at the maspin promoter. Treatment with 5-aza-2'-deoxycytidine did not activate maspin expression in these five maspin-negative HCC cell lines, whereas treatment with Trichostatin A (TSA) activated maspin expression in two of them. Treatment with TSA increased histone acetylation in some HCC cell lines. These results suggest that aberrant maspin expression in biliary tract carcinomas is closely associated with demethylation at the promoter region, but that some HCC cell lines additionally require histone acetylation. In addition, the fact that maspin-negative HCC cell lines remain after treatment with TSA suggests the existence of other repressive factors controlling maspin expression.

Topics: Acetylation; Bile Duct Neoplasms; Carcinoma; Cell Line, Tumor; Chromatin; DNA Methylation; Epigenesis, Genetic; Female; Genes, Tumor Suppressor; Humans; Hydroxamic Acids; Immunohistochemistry; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Precipitin Tests; Promoter Regions, Genetic; Protein Synthesis Inhibitors; Proteins; RNA, Messenger; Sequence Analysis, DNA; Serpins