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

著者

    • Inoue, Takeshi
    • Anai, Satoshi
    • Onishi, Sayuri
    • Miyake, Makito
    • Tanaka, Nobumichi
    • Hirayama, Akihide
    • Fujimoto, Kiyohide
    • Hirao, Yoshihiko

書誌事項

タイトル

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

タイトル別名

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

著者名

Inoue, Takeshi

著者名

Anai, Satoshi

著者名

Onishi, Sayuri

著者名

Miyake, Makito

著者名

Tanaka, Nobumichi

著者名

Hirayama, Akihide

著者名

Fujimoto, Kiyohide

著者名

Hirao, Yoshihiko

学位授与大学

奈良県立医科大学

取得学位

博士(医学)

学位授与番号

甲第606号

学位授与年月日

2013-01-05

注記・抄録

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.

開始ページ : 13:1

PubMed番号 : http://www.ncbi.nlm.nih.gov/pubmed/23289871

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各種コード

  • NII論文ID(NAID)
    500000731224
  • NII著者ID(NRID)
    • 8000000907296
    • 8000000907297
    • 8000000907298
    • 8000000907299
    • 8000000907300
    • 8000000907301
    • 8000000907302
    • 8000000907303
  • DOI(出版社)
  • DOI
  • 本文言語コード
    • eng
  • データ提供元
    • 機関リポジトリ
    • NDLデジタルコレクション
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