論文 - 詳細
| RRC ID | 43771 |
|---|---|
| 著者 | Takeba Y, Matsumoto N, Watanabe M, Takenoshita-Nakaya S, Ohta Y, Kumai T, Takagi M, Koizumi S, Asakura T, Otsubo T. |
| タイトル | The Rho kinase inhibitor fasudil is involved in p53-mediated apoptosis in human hepatocellular carcinoma cells. |
| ジャーナル | Cancer Chemother Pharmacol |
| Abstract |
PURPOSE:Rho kinase is an important factor in tumor progression. We demonstrated that Rho kinase-associated coil-containing protein kinase (ROCK) is expressed in hepatic tissues in hepatocellular carcinoma (HCC) and confirmed its roles in cell survival in HCC cells using the ROCK inhibitor, fasudil. METHODS:ROCK protein levels were estimated in hepatic tissues with HCC compared with healthy liver tissues or hepatic hemangioma tissues using immunohistochemistry. Furthermore, HepG2 and Huh7 cells were cultured with ROCK inhibitor, fasudil for 24 h in vitro. Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay, and apoptotic cells were detected by cell death ELISA. The expression apoptosis-related proteins were analyzed using Western blotting. RESULTS:Fasudil significantly decreased cell proliferation and induced apoptosis mediated by increases in p53, Bax, caspase-9, and caspase-3 in HepG2 and Huh7 cells. The induction of apoptosis was inhibited in HCC cells precultured with p53 decoy oligodeoxynucleotide. CONCLUSION:These results suggest that ROCK inhibits the p53-mediated apoptosis pathway in HCC. Fasudil may thus be a beneficial approach to HCC therapy. |
| 巻・号 | 69(6) |
| ページ | 1545-55 |
| 公開日 | 2012-6-1 |
| DOI | 10.1007/s00280-012-1862-6 |
| PMID | 22481618 |
| MeSH | 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives* 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology Apoptosis / drug effects* Carcinoma, Hepatocellular / drug therapy* Carcinoma, Hepatocellular / pathology Cell Line, Tumor Cell Proliferation / drug effects Humans Liver / enzymology Liver Neoplasms / drug therapy* Liver Neoplasms / pathology Protein Kinase Inhibitors / pharmacology* Tumor Suppressor Protein p53 / physiology* rho-Associated Kinases / analysis rho-Associated Kinases / antagonists & inhibitors* rho-Associated Kinases / physiology |
| IF | 2.967 |
| 引用数 | 19 |
| WOS 分野 | PHARMACOLOGY & PHARMACY ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | HuH-7 Hep G2 |