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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 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Inhibition of RSK/YB-1 signaling enhances the anti-cancer effect of enzalutamide in prostate cancer. |
| 掲載誌名 | 正式名：The Prostate 略 称：Prostate ISSNコード：10970045/02704137 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 74(9),pp.959-69 |
| 著者・共著者 | Masaki Shiota, Akira Yokomizo, Ario Takeuchi, Momoe Itsumi, Kenjiro Imada, Eiji Kashiwagi, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Seiji Naito |
| 発行年月 | 2014/06 |
| 概要 | BACKGROUND:Previously, we have shown that Y-box binding protein-1 (YB-1) regulates androgen receptor (AR) expression and contributes to castration resistance. However, the mechanism of YB-1 activation remains unknown. In this study, we aimed to elucidate the mechanism and role of YB-1 activation in relation to castration resistance as well as enzalutamide resistance, with a view to developing a novel therapeutic concept for castration-resistant prostate cancer (CRPC) treatment.METHODS:The expression and phosphorylation levels of ribosomal S6 kinase 1 (RSK1), YB-1 and AR were examined by quantitative PCR and Western blotting using prostate cancer cells. In addition, the effects of YB-1 inhibition using specific siRNA and small molecule inhibitor SL0101 on AR expression as well as combination treatment with enzalutamide and SL0101 were examined.RESULTS:We found that androgen deprivation, as well as treatment with the next-generation anti-androgen enzalutamide, induced RSK1 and YB-1 activation followed by AR induction, which could be reversed by YB-1 shutdown and RSK inhibitor SL0101. SL0101 and enzalutamide exerted a synergistic tumor-suppressive effect on cell proliferation in androgen-dependent prostate cancer LNCaP cells, as well as castration-resistant C4-2 cells. Furthermore, the phosphorylation levels of RSK1 and YB-1 were elevated in castration- and enzalutamide-resistant cells, compared with their parental cells.CONCLUSIONS:Taken together, these findings indicate that RSK1/YB-1 signaling contributes to castration as well as enzalutamide resistance, and that the therapeutic targeting of RSK1/YB-1 signaling would be a promising novel therapy against prostate cancer, especially CRPC when combined with enzalutamide. |
| DOI | 10.1002/pros.22813 |
| PMID | 24740858 |