Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model

• Material Type: 博士論文
• Title: Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model
• Author/Editor: Inoue, Takeshi; Anai, Satoshi; Onishi, Sayuri; Miyake, Makito; Tanaka, Nobumichi; Hirayama, Akihide; Fujimoto, Kiyohide; Hirao, Yoshihiko
• Author Heading: Inoue, Takeshi; Anai, Satoshi; Onishi, Sayuri; Miyake, Makito; Tanaka, Nobumichi; Hirayama, Akihide; Fujimoto, Kiyohide; Hirao, Yoshihiko
• Publication, Distribution, etc.: BioMed Central
• Publication Date: 2013-01-05
• Publication Date (W3CDTF): 2013-01-05
• Alternative Title: 前立腺癌マウスモデルにおけるジクロフェナク局所投与によるCOX-2発現の阻害はTRAILの増幅を介して放射線感受性を増強させる
• Periodical title: BMC urology
• No. or year of volume/issue: 13
• Volume: 13
• Pages: Article No.1-
• ISSN (Periodical Title): ISSN : 1471-2490
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2013-11-27
• Dissertation Number: 甲第606号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Prostate cancer; Radiation therapy; COX-2; TRAIL; Apoptosis; Topical therapy; Radiosensitizer; Diclofenac; Radioresistance
• Target Audience: 一般
• Note (General): type:Thesis; BACKGROUND: COX-2 inhibitors have an antitumor potential and have been verified by many researchers. Treatment of cancer cells with external stressors such as irradiation can stimulate the over-expression of COX-2 and possibly confer radiation resistance. In this study, we tested if topical diclofenac, which inhibits both COX-1 and COX-2, administration rendered prostate tumor cells sensitize to the effects of radiation. METHODS: LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 1000 μM diclofenac. Next, a clonogenic assay was performed in which cells were subjected to irradiation (0 to 4 Gy) with or without diclofenac. COX-2 expression and other relevant molecules were measured by real-time PCR and immunohistochemistry after irradiation and diclofenac treatment. In addition, we assessed the tumor volumes of xenograft LNCaP-COX-2 cells treated with topical diclofenac with or without radiation therapy (RT). RESULTS: LNCaP-COX-2 and LNCaP-Neo cell lines experienced cytotoxic effects of diclofenac in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to RT than LNCaP-Neo cells. Furthermore, the addition of diclofenac sensitized LNCaP-COX-2 not but LNCaP-Neo cells to the cytocidal effects of radiation. In LNCaP-COX-2 cells, diclofenac enhanced radiation-induced apoptosis compared with RT alone. This phenomenon might be attributed to enhancement of RT-induced TRAIL expression as demonstrated by real-time PCR analysis. Lastly, tumor volumes of LNCaP-COX-2 cells xenograft treated with diclofenac or RT alone was >4-fold higher than in mice treated with combined diclofenac and radiation (p<0.05). CONCLUSIONS: These in vitro and in vivo findings suggest that conventional COX inhibitor, diclofenac enhances the effect of RT on prostate cancer cells that express COX-2. Thus, diclofenac may have potential as radiosensitizer for treatment of prostate cancer.; 博士（医学）・甲第606号・平成25年11月27日; © 2013 Inoue et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.; identifier:BMC urology Vol.13 Article No.1 (2013 Jan); identifier:14712490; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2671; identifier:BMC urology, 13: Article No.1
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1186/1471-2490-13-1
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2671/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

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