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August 2012 Volume 41 Issue 2

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Article

REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer

  • Authors:
    • Takeshi Hirata
    • Masami Watanabe
    • Haruki Kaku
    • Yasuyuki Kobayashi
    • Hiroshi Yamada
    • Masakiyo Sakaguchi
    • Kohji Takei
    • Nam-Ho Huh
    • Yasutomo Nasu
    • Hiromi Kumon
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan, Center for Gene and Cell Therapy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan, Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan, Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
  • Pages: 559-564
    |
    Published online on: May 31, 2012
       https://doi.org/10.3892/ijo.2012.1503
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Abstract

Bladder cancer is one of the most common urogenital malignancies. The intravesical instillation of anticancer agents is an attractive strategy to treat a superficial lesion or floating/disseminated cancer cells after transurethral operation. An adenovirus carrying REIC/Dkk-3, a tumor suppressor gene (Ad-REIC), exhibits cancer-specific apoptotic effects in various types of cancer cells. The aim of the present study was to examine the potential of Ad-REIC as a therapeutic agent for bladder cancer. KK47 and RT4 human bladder cancer cells were sensitive to the Ad-REIC treatment for apoptosis induction, but some human bladder cancer cell lines (T24, J82 and TccSup) were resistant. Significant cell growth inhibition was observed when these resistant cancer cell lines were treated with Ad-REIC in a condition of floating cells, which is clinically observed after transurethral operation and becomes a cause of intravesical cancer dissemination. The therapeutic potential of Ad-REIC for the treatment of multidrug-resistant bladder cancer was investigated. The adriamycin-resistant KK47 bladder cancer cells (KK47/ADM), which also present multidrug resistance, showed induction of significant apoptosis following Ad-REIC treatment. The Ad-REIC treatment induced downregulation of P-glycoprotein in KK47/ADM cells and restored the sensitivity to doxorubicin (adriamycin). Ad-REIC suppressed P-glycoprotein expression in a c-Jun-NH2-kinase (JNK)-dependent manner. Therefore, the current study indicated two therapeutic aspects of the Ad-REIC agent against human bladder cancer cells, as an apoptosis inducer/cell growth inhibitor and as a sensitizer of chemotherapeutic agents in multidrug-resistant cancer cells. The intravesical instillation of Ad-REIC could be an attractive therapeutic method in human bladder cancer where the treatment of superficial lesions and floating/disseminated or multidrug-resistant cancer cells is necessary.
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Copy and paste a formatted citation
Spandidos Publications style
Hirata T, Watanabe M, Kaku H, Kobayashi Y, Yamada H, Sakaguchi M, Takei K, Huh N, Nasu Y, Kumon H, Kumon H, et al: REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer. Int J Oncol 41: 559-564, 2012.
APA
Hirata, T., Watanabe, M., Kaku, H., Kobayashi, Y., Yamada, H., Sakaguchi, M. ... Kumon, H. (2012). REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer. International Journal of Oncology, 41, 559-564. https://doi.org/10.3892/ijo.2012.1503
MLA
Hirata, T., Watanabe, M., Kaku, H., Kobayashi, Y., Yamada, H., Sakaguchi, M., Takei, K., Huh, N., Nasu, Y., Kumon, H."REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer". International Journal of Oncology 41.2 (2012): 559-564.
Chicago
Hirata, T., Watanabe, M., Kaku, H., Kobayashi, Y., Yamada, H., Sakaguchi, M., Takei, K., Huh, N., Nasu, Y., Kumon, H."REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer". International Journal of Oncology 41, no. 2 (2012): 559-564. https://doi.org/10.3892/ijo.2012.1503
Copy and paste a formatted citation
x
Spandidos Publications style
Hirata T, Watanabe M, Kaku H, Kobayashi Y, Yamada H, Sakaguchi M, Takei K, Huh N, Nasu Y, Kumon H, Kumon H, et al: REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer. Int J Oncol 41: 559-564, 2012.
APA
Hirata, T., Watanabe, M., Kaku, H., Kobayashi, Y., Yamada, H., Sakaguchi, M. ... Kumon, H. (2012). REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer. International Journal of Oncology, 41, 559-564. https://doi.org/10.3892/ijo.2012.1503
MLA
Hirata, T., Watanabe, M., Kaku, H., Kobayashi, Y., Yamada, H., Sakaguchi, M., Takei, K., Huh, N., Nasu, Y., Kumon, H."REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer". International Journal of Oncology 41.2 (2012): 559-564.
Chicago
Hirata, T., Watanabe, M., Kaku, H., Kobayashi, Y., Yamada, H., Sakaguchi, M., Takei, K., Huh, N., Nasu, Y., Kumon, H."REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer". International Journal of Oncology 41, no. 2 (2012): 559-564. https://doi.org/10.3892/ijo.2012.1503
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