|
イツミ モモエ
逸見 百江 所属 川崎医科大学 医学部 一般教養 自然科学 職種 助教 |
|
| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Sensitivity of doxorubicin-resistant cells to sorafenib: possible role for inhibition of eukaryotic initiation factor-2alpha phosphorylation. |
| 掲載誌名 | 正式名：International journal of oncology 略 称：Int J Oncol ISSNコード：17912423/10196439 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 37(2),pp.509-17 |
| 著者・共著者 | Masaki Shiota, Masatoshi Eto, Akira Yokomizo, Yasuhiro Tada, Ario Takeuchi, Momoe Itsumi, Katsunori Tatsugami, Takeshi Uchiumi, Seiji Naito |
| 発行年月 | 2010/08 |
| 概要 | Patients with advanced cancer including breast cancer, hepatocellular cancer and urothelial cancer frequently receive a chemotherapy regimen containing doxorubicin. However, doxorubicin-resistance is a major obstacle for cancer chemotherapy. Recently, several molecular-targeted agents have become available. Sorafenib (BAY 43-9006) is known to target multiple kinases and has demonstrated activity in renal cell and hepatocellular cancer. In this study, sorafenib was found to inhibit phosphorylation of the eukaryotic initiation factor-2alpha (eIF2alpha), induce cell cycle arrest at G2 phase and increase cellular apoptosis in doxorubicin-resistant human urothelial cell lines. An eIF2alpha kinase, PERK was responsible for eIF2alpha phosphorylation and PERK knockdown induced cellular apoptosis similar to sorafenib treatment in doxorubicin-resistant cancer cells. Furthermore, sorafenib sensitized doxorubicin-resistant cancer cells, but not their parental cells to oxidative stress exerted by both hydrogen peroxide and doxorubicin. In addition, PERK knockdown sensitized doxorubicin-resistant cancer cells to oxidative stress. In conclusion, PERK inhibition using sorafenib with or without doxorubicin might be a promising therapeutic approach for doxorubicin-resistant cancers retaining high phosphorylation levels of eIF2alpha. |
| DOI | 10.3892/ijo_00000700 |
| PMID | 20596679 |