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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2671

Title: Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model
Other Titles: 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
Authors: Inoue, Takeshi
Anai, Satoshi
Onishi, Sayuri
Miyake, Makito
Tanaka, Nobumichi
Hirayama, Akihide
Fujimoto, Kiyohide
Hirao, Yoshihiko
Keywords: Prostate cancer
Radiation therapy
COX-2
TRAIL
Apoptosis
Topical therapy
Radiosensitizer
Diclofenac
Radioresistance
Issue Date: 5-Jan-2013
Publisher: BioMed Central
Citation: BMC urology Vol.13 January p.13:1 doi;10.1186/1471-2490-13-1
Abstract: 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.
Description: 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.
URI: http://hdl.handle.net/10564/2671
ISSN: 14712490
Academic Degrees and number: 24601A606
Degree-granting date: 2013-11-27
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2013年度

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