Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium butyrate is a short-chain fatty acid produced by fermentation in the gastrointestinal tract. It induces differentiation of several kinds of cancer by inhibiting histone deacetylase activity. We have reported that butyrate stimulates hepatocellular carcinoma cells into their normal phenotype. Since sodium butyrate affects both differentiation and apoptosis, we investigated expression of bcl-2-related genes in a human hepatocellular carcinoma cell line HCC-T. The expression of anti-apoptotic Bcl-2 and Mcl-1/EAT was up-regulated 4 h after the treatment, while pro-apoptotic Bax expression did not change. Gene expressions in the early stage of butyrate-stimulation were investigated by the differential display assay and the cDNA expression array. Laminin and keratin 18 were increased 6 h after the stimulation with sodium butyrate. The results of cDNA expression array revealed up-regulation of cell cycle inhibitory genes such as cyclin-dependent kinase 4 inhibitor, and interferon-related genes such as STAT2 and 3, while down-regulation of cyclin-dependent kinase 2 and cyclin E. Up-regulated production of p21WAF-1 and Mcl-1/EAT was also confirmed by Western blotting. The cytoskeletal change indicated by up-regulation of laminin and keratin 18 may be an important factor in the decrease in malignant phenotype of cancer cells. Up-regulation of interferon-related genes indicated that butyrate-treatment might induce a similar phenotypic change to that induced by type 1 interferons. This study suggests several target genes for the future gene therapy of cancer or genes preventing cancer development from pre-malignant tissues.
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PMID:Gene expression associated with the decrease in malignant phenotype of human liver cancer cells following stimulation with a histone deacetylase inhibitor. 1558 45

Hepatitis B virus X (HBx), a viral onco-protein encoded by HBV, can promote oncogenesis of HCC. However, the mechanism of HBx in hepatocarcinogenesis is still unclear. In this study, we establish a new mouse model with normal immune system to investigate the role of HBx and its functional mechanisms under normal immune function. The animal model was established by injecting HBx-EGFP-14-19 cells into the hepatic portal vein of KM mice. To verify the mouse model, the expression of HBx in the liver tissue of mice was detected by qRT-PCR, western blotting and immunohistochemistry. The apoptosis index was calculated using the terminal deoxynucleotidyl transferase-dUTP nick-end labeling (TUNEL) assay, and the expression levels of apoptosis-related and cell cycle-related factors were measured. Moreover, expression of proteins in the protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling pathway was detected in HBx-EGFP-14-19 mice with and without use of an Akt inhibitor. The results showed the HBx was successfully overexpressed in liver of KM mice. After overexpressing HBx, the apoptosis index was downregulated in HBx-EGFP-14-19 liver tissue, and the expression levels of caspase-9 and Bad were reduced, but Bcl-xl was increased in HBx-EGFP-14-19 liver tissue. Overexpression of HBx increased the expression of the cyclin-dependent kinase 2 (CDK2), cyclinD1 and cyclinE. Moreover, compared with the low-level HBx group, p-Akt and p-mTOR were increased in the livers of mice with high levels of HBx. However, inactivation of apoptosis by overexpression of HBx was abolished by the treatment with an Akt inhibitor. These results indicate that HBx can induce anti-apoptosis mechanisms in hepatocytes in vivo, which is mediated by the Akt/mTOR signaling pathway.
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PMID:Hepatitis B virus X reduces hepatocyte apoptosis and promotes cell cycle progression through the Akt/mTOR pathway in vivo. 3063 95