Combination of non-viral connexin 43 gene therapy and docetaxel inhibits the growth of human prostate cancer in mice

  • Authors:
    • Masayoshi Fukushima
    • Yoshiyuki Hattori
    • Takashi Yoshizawa
    • Yoshie Maitani
  • View Affiliations

  • Published online on: January 1, 2007     https://doi.org/10.3892/ijo.30.1.225
  • Pages: 225-231
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Abstract

Docetaxel (DTX) is used for the treatment of advanced hormone refractory prostate cancer. Connexin 43 (Cx43) is a tumor suppressor gene, and transfection of the Cx43 gene increases sensitivity to several chemotherapeutic agents. The objective of this study was to evaluate the effectiveness of combination therapy of Cx43-expressing plasmid DNA (pCMV-Cx43) and DTX both in vitro and in vivo using a non-viral vector in human prostate cancer PC-3 cells. Transfection of pCMV-Cx43 into the cells neither inhibited tumor growth nor increased gap junctional intercellular communication; however, combination therapy of pCMV-Cx43 and DTX significantly inhibited cell growth. Forced expression of Cx43 in the cells induced apoptotic cells by down-regulation of Bcl-2 expression and significantly more up-regulation of caspase-3 activity than either treatment alone. The combination of repeated intratumoral injection of pCMV-Cx43 (10 µg/tumor) with non-viral vector and a single intravenous injection of DTX (15 mg/kg) was compared with a repeated injection of Cx43 alone and a single injection of DTX alone on PC-3 tumor xenografts. Significant antitumoral effects were observed in mice receiving combined treatment, compared with DTX alone. The data presented here provide a rational strategy for treating patients with advanced hormone refractory prostate cancer.

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January 2007
Volume 30 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Fukushima M, Hattori Y, Yoshizawa T and Maitani Y: Combination of non-viral connexin 43 gene therapy and docetaxel inhibits the growth of human prostate cancer in mice. Int J Oncol 30: 225-231, 2007.
APA
Fukushima, M., Hattori, Y., Yoshizawa, T., & Maitani, Y. (2007). Combination of non-viral connexin 43 gene therapy and docetaxel inhibits the growth of human prostate cancer in mice. International Journal of Oncology, 30, 225-231. https://doi.org/10.3892/ijo.30.1.225
MLA
Fukushima, M., Hattori, Y., Yoshizawa, T., Maitani, Y."Combination of non-viral connexin 43 gene therapy and docetaxel inhibits the growth of human prostate cancer in mice". International Journal of Oncology 30.1 (2007): 225-231.
Chicago
Fukushima, M., Hattori, Y., Yoshizawa, T., Maitani, Y."Combination of non-viral connexin 43 gene therapy and docetaxel inhibits the growth of human prostate cancer in mice". International Journal of Oncology 30, no. 1 (2007): 225-231. https://doi.org/10.3892/ijo.30.1.225