論文 - 詳細
| RRC ID | 67738 |
|---|---|
| 著者 | Li CF, Tsai HH, Ko CY, Pan YC, Yen CJ, Lai HY, Yuh CH, Wu WC, Wang JM. |
| タイトル | HMDB and 5-AzadC Combination Reverses Tumor Suppressor CCAAT/Enhancer-Binding Protein Delta to Strengthen the Death of Liver Cancer Cells. |
| ジャーナル | Mol Cancer Ther |
| Abstract |
Hepatocellular carcinoma (HCC) can arise from chronic inflammation due to viral infection, organ damage, drug toxicity, or alcohol abuse. Moreover, gene desensitization via aberrant CpG island methylation is a frequent epigenetic defect in HCC. However, the details of how inflammation is linked with epigenetic-mediated desensitization of tumor suppressor genes remains less investigated. In this study, we found that loss of CEBPD enhances the growth of liver cancer cells and is associated with the occurrence of liver cancers, as determined by the assessment of clinical specimens and in vivo animal models. Moreover, E2F1-regulated epigenetic axis attenuated CEBPD expression in liver cancer cells. CEBPD is responsive to the hydroxymethyldibenzoylmethane (HMDB)-induced p38/CREB pathway and plays an important role in the HMDB-induced apoptosis of cancer cells. Regarding depression of epigenetic effects to enhance HMDB-induced CEBPD expression, the combination of HMDB and 5-Aza-2'-deoxycytidine (5-AzadC) could enhance the death of liver cancer cells and reduce the tumor formation of Huh7 xenograft mice. In conclusion, these results suggest that CEBPD could be a useful diagnostic marker and therapeutic target in HCC. The results also reveal the therapeutic potential for low-dose 5-AzadC to enhance the HMDB-induced death of HCC cells. |
| 巻・号 | 14(11) |
| ページ | 2623-33 |
| 公開日 | 2015-11-1 |
| DOI | 10.1158/1535-7163.MCT-15-0025 |
| PII | 1535-7163.MCT-15-0025 |
| PMID | 26358750 |
| MeSH | Animals Antineoplastic Combined Chemotherapy Protocols / pharmacology* Apoptosis / drug effects Apoptosis / genetics Azacitidine / administration & dosage Azacitidine / analogs & derivatives* Azacitidine / pharmacology Blotting, Western CCAAT-Enhancer-Binding Protein-delta / antagonists & inhibitors* CCAAT-Enhancer-Binding Protein-delta / genetics CCAAT-Enhancer-Binding Protein-delta / metabolism Carcinoma, Hepatocellular / drug therapy* Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism Cell Line, Tumor Cells, Cultured Decitabine E2F1 Transcription Factor / genetics E2F1 Transcription Factor / metabolism Gene Expression Profiling / methods Gene Expression Regulation, Neoplastic / drug effects Hep G2 Cells Humans Immunohistochemistry Ketones / administration & dosage Ketones / pharmacology* Liver Neoplasms / drug therapy* Liver Neoplasms / genetics Liver Neoplasms / metabolism Mice, Inbred NOD Mice, SCID Oligonucleotide Array Sequence Analysis Propane / administration & dosage Propane / analogs & derivatives* Propane / pharmacology RNA Interference Reverse Transcriptase Polymerase Chain Reaction Tumor Burden / drug effects Tumor Burden / genetics Xenograft Model Antitumor Assays |
| IF | 5.615 |
| リソース情報 | |
| ヒト・動物細胞 | HuH-7 |