Adenovirus-mediated gene transduction of truncated IκBα enhances radiosensitivity in human colon cancer cells

Tomohide Mukogawa, Fumikazu Koyama, Masaaki Tachibana, Atsushi Takayanagi, Nobuyoshi Shimizu, Hisao Fujii, Masato Ueno, Hiroshi Matsumoto, Taku Takeuchi, Yoshiyuki Nakajima

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28 Citations (Scopus)

Abstract

Nuclear factor kappa B (NF-κB) is a transcription factor that is known to regulate apoptosis when cells are exposed to DNA-damaging agents such as ionizing radiation and cytotoxic drugs. We sought to determine if inhibition of NF-κB could enhance radiosensitivity in human colon cancer cells in vitro and in vivo. To inhibit NF-κB activation specifically, we constructed a recombinant adenovirus vector expressing a truncated form of the inhibitor protein IκBα (IκBαΔN) that lacks the phosphorylation sites essential for activation of NF-κB, and transfected two human colon cancer cell lines (HT29 and HCT15) with this vector. In vitro colony-forming assays revealed that the overexpression of the stable IκBα by AXIκBαΔN infection significantly suppressed cell growth after irradiation in both cell lines as compared to infection with a control vector, AxLacZ. Treatment with AxIκBαΔN and irradiation successfully inhibited the growth of HT29 xenografted subcutaneous tumors in nude mice with an 83.8% volume reduction on day 38 as compared to the untreated tumors. Furthermore, it was demonstrated that apoptosis was increased by adenovirus-mediated gene transduction of IκBαΔN in vitro and in vivo. These results indicated that inhibition of NF-κB could enhance radiosensitivity through an increase in radiation-induced apoptosis. We believe that radio-gene therapy using adenovirus-mediated gene transduction of IκBαΔN could be an attractive candidate as a treatment strategy for colorectal cancer.

Original languageEnglish
Pages (from-to)745-750
Number of pages6
JournalCancer science
Volume94
Issue number8
DOIs
Publication statusPublished - 2003 Aug 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Mukogawa, T., Koyama, F., Tachibana, M., Takayanagi, A., Shimizu, N., Fujii, H., Ueno, M., Matsumoto, H., Takeuchi, T., & Nakajima, Y. (2003). Adenovirus-mediated gene transduction of truncated IκBα enhances radiosensitivity in human colon cancer cells. Cancer science, 94(8), 745-750. https://doi.org/10.1111/j.1349-7006.2003.tb01513.x