論文 - 詳細
| RRC ID | 43007 |
|---|---|
| 著者 | Sato H, Fukumoto K, Hada S, Hagiwara H, Fujimoto E, Negishi E, Ueno K, Yano T. |
| タイトル | Enhancing effect of connexin 32 gene on vinorelbine-induced cytotoxicity in A549 lung adenocarcinoma cells. |
| ジャーナル | Cancer Chemother Pharmacol |
| Abstract |
PURPOSE:Connexin (Cx) genes exert negative growth effects on tumor cells with certain cell specificity, and tumor-suppressive effects of the Cx genes contribute to enhancement of chemotherapeutical agents-induced cytotoxicity in some cancer cells. Since we and others have been reported that Cx32 acts as a tumor suppressor gene in lung adenocarcinomas, this study was undertaken to estimate if the combination of Cx32-dependent tumor-suppressive effect and vinorelbine (VBN), a chemotherapeutic agent which has been utilized for clinical lung adenocarcinoma treatment, could be effective in enhancing the sensitivity of the lung cancer to VBN treatment. METHODS:We established the A549 cells (a human lung adenocarcinoma cell line) which had stable expression of Cx32 and estimated effect of Cx32 on VBN-induced cytotoxicity in the established cells. RESULTS:Cx32 expression in A549 cells significantly potentiated VBN-induced cytotoxicity on the cells due to enhancement of apoptosis induction. The enhancing cytotoxicity in A549 cells by Cx32 mainly depended on a decrease in expression of multi-drug resistance-1 (MDR-1) gene responsible for reduction of VBN accumulation into the cells. We also observed that silencing of Cx32 by siRNA treatment elevated the expression level of MDR-1 mRNA in A549 cells and that inhibition of MDR-1 gene product-dependent function enhanced VBN-induced cytotoxicity in the cells. CONCLUSION:These results suggest that Cx32 contributes to the enhancement of VBN-induced cytotoxicity in A549 cells via the reduction of MDR-1 expression. |
| 巻・号 | 60(3) |
| ページ | 449-57 |
| 公開日 | 2007-8-1 |
| DOI | 10.1007/s00280-006-0406-3 |
| PMID | 17569045 |
| MeSH | Adenocarcinoma / genetics* Adenocarcinoma / pathology Apoptosis / drug effects Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / pathology Cell Cycle / drug effects Cell Line, Tumor Cell Survival / drug effects Connexins / drug effects Connexins / genetics* DNA, Neoplasm / drug effects DNA, Neoplasm / genetics Gene Expression Regulation, Neoplastic / drug effects Glycyrrhetinic Acid / pharmacology* Humans Lung Neoplasms / genetics* Lung Neoplasms / pathology RNA, Messenger / genetics |
| IF | 2.967 |
| 引用数 | 20 |
| WOS 分野 | PHARMACOLOGY & PHARMACY ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | |