論文 - 詳細
| RRC ID | 44378 |
|---|---|
| 著者 | Morisaki T, Umebayashi M, Kiyota A, Koya N, Tanaka H, Onishi H, Katano M. |
| タイトル | Combining celecoxib with sorafenib synergistically inhibits hepatocellular carcinoma cells in vitro. |
| ジャーナル | Anticancer Res |
| Abstract |
AIM:Sorafenib is a promising treatment for hepatocellular carcinoma (HCC) but recent toxicity concerns suggest that new strategies for its use are needed. One approach for reducing toxicity is to use lower doses of sorafenib in combination with other complementary mechanisms. Celecoxib, a cyclooxygenase-2 inhibitor, has been shown to inhibit HCC, and we hypothesized that low-dose sorafenib co-administered with celecoxib could act synergistically in the inhibition of HCC. In this study, the effect of sorafenib was tested in combination with celecoxib on the growth of human HCC cells in vitro. MATERIALS AND METHODS:Two human HCC cell lines, HepG2 and Huh7, were treated with sorafenib and celecoxib, alone and in combination, and the effect of these treatments on growth, apoptosis, and expression of phospho-AKT was evaluated by WST-8, DNA content, and immunocytochemical assays, respectively. RESULTS:When compared to the actions of either agent alone, the combination of low concentrations of sorafenib (<5 μM) and celecoxib (<20 μM) resulted in enhanced inhibition of both cell growth and AKT activation, and increased the induction of apoptosis. Combination index (CI) analysis showed that the growth inhibition effect was synergistic. CONCLUSION:This study shows that celecoxib synergistically potentiates the sorafenib-mediated antitumor effect. This finding establishes the foundation for clinical trials evaluating the efficacy of co-administration of soerafenib and celecoxib as a treatment for HCC. |
| 巻・号 | 33(4) |
| ページ | 1387-95 |
| 公開日 | 2013-4-1 |
| PII | 33/4/1387 |
| PMID | 23564777 |
| MeSH | Antineoplastic Combined Chemotherapy Protocols / pharmacology* Apoptosis / drug effects* Blotting, Western Carcinoma, Hepatocellular / drug therapy* Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / pathology Celecoxib Cell Proliferation / drug effects* Dinoprostone / metabolism Drug Synergism Fluorescent Antibody Technique Humans In Vitro Techniques Liver Neoplasms / drug therapy* Liver Neoplasms / metabolism Liver Neoplasms / pathology Niacinamide / administration & dosage Niacinamide / analogs & derivatives Phenylurea Compounds / administration & dosage Phosphorylation / drug effects Proto-Oncogene Proteins c-akt / metabolism Pyrazoles / administration & dosage Sorafenib Sulfonamides / administration & dosage Tumor Cells, Cultured |
| IF | 1.994 |
| 引用数 | 28 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2 HuH-7 |