論文 - 詳細
| RRC ID | 62733 |
|---|---|
| 著者 | Takeda H, Okada M, Suzuki S, Kuramoto K, Sakaki H, Watarai H, Sanomachi T, Seino S, Yoshioka T, Kitanaka C. |
| タイトル | Rho-Associated Protein Kinase (ROCK) Inhibitors Inhibit Survivin Expression and Sensitize Pancreatic Cancer Stem Cells to Gemcitabine. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND:Targeting pathways regulating survivin expression, which has been implicated in multidrug resistance of cancer cells, is a promising strategy to overcome cancer chemoresistance. To date, the role of rho-associated protein kinases (ROCKs) in survivin expression remains largely unknown. MATERIALS AND METHODS:The effects of ROCK inhibitors Y-27632 and fasudil on survivin expression and cell viability were determined by immunoblot analysis and dye exclusion, respectively, in PANC-1 CSLC, a cancer stem cell line derived from a serum-cultured, gemcitabine-sensitive pancreatic cancer cell line, PANC-1. RESULTS:siRNA-mediated knockdown of survivin revealed that the gemcitabine resistance of PANC-1 CSLC was dependent on survivin expression. Both Y-27632 and fasudil, reduced survivin expression in PANC-1 CSLC cells and sensitized them to gemcitabine. ROCK inhibition also reduced survivin expression in various other human cancer cell lines. CONCLUSION:Small molecule inhibitor-mediated targeting of ROCK may be a viable strategy to overcome cancer chemoresistance through down-regulation of survivin. |
| 巻・号 | 36(12) |
| ページ | 6311-6318 |
| 公開日 | 2016-12-1 |
| DOI | 10.21873/anticanres.11227 |
| PII | 36/12/6311 |
| PMID | 27919951 |
| MeSH | Antimetabolites, Antineoplastic / pharmacology* Deoxycytidine / analogs & derivatives* Deoxycytidine / pharmacology Drug Synergism Gemcitabine Humans Inhibitor of Apoptosis Proteins / metabolism* Neoplastic Stem Cells / drug effects* Neoplastic Stem Cells / metabolism Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology* Protein Kinase Inhibitors / pharmacology* Survivin rho-Associated Kinases / antagonists & inhibitors* |
| IF | 1.994 |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) |