Gene therapy for colorectal cancer by adenovirus-mediated siRNA targeting CD147 based on loss of the IGF2 imprinting system

  • Authors:
    • Yuqin Pan
    • Bangshun He
    • Jie Chen
    • Huiling Sun
    • Qiwen Deng
    • Feng Wang
    • Houqun Ying
    • Xian Liu
    • Kang Lin
    • Hongxin Peng
    • Hongguang Xie
    • Shukui Wang
  • View Affiliations

  • Published online on: September 23, 2015     https://doi.org/10.3892/ijo.2015.3181
  • Pages: 1881-1889
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Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality phenomenon in CRC. Recently observed association of CRC with cluster of differentiation 147 (CD147) could provide a novel approach for gene therapy. In the present study, we investigated the feasibility of using adenovirus‑mediated siRNA targeting CD147 based on the IGF2 LOI system for targeted gene therapy of CRC. A novel adenovirus-mediated siRNA targeting CD147, rAd-H19-CD147mirsh, which was driven by the IGF2 imprinting system, was constructed. The results showed that the EGFP expression was detected only in the IGF2 LOI cell lines (HT-29 and HCT-8), but that no EGFP was produced in cell lines with maintenance of imprinting (MOI) (HCT116). Moreover, rAd-H19-CD147mirsh significantly inhibited the expression of CD147, decreased cell viability and invasive ability, and increased sensitivity to chemotherapeutic drugs only in the LOI cell lines in vitro. Furthermore, mice bearing HT-29 xenografted tumors, which received intratumoral administration of the rAd-H19-CD147mirsh, showed significantly reduced tumor growth and enhanced survival. We conclude that recombinant adenovirus-mediated siRNA targeting CD147 based on the IGF2 LOI system inhibited the growth of the LOI cells in vitro and in vivo, which would provide a novel approach for targeted CRC gene therapy.
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November-2015
Volume 47 Issue 5

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

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Spandidos Publications style
Pan Y, He B, Chen J, Sun H, Deng Q, Wang F, Ying H, Liu X, Lin K, Peng H, Peng H, et al: Gene therapy for colorectal cancer by adenovirus-mediated siRNA targeting CD147 based on loss of the IGF2 imprinting system. Int J Oncol 47: 1881-1889, 2015
APA
Pan, Y., He, B., Chen, J., Sun, H., Deng, Q., Wang, F. ... Wang, S. (2015). Gene therapy for colorectal cancer by adenovirus-mediated siRNA targeting CD147 based on loss of the IGF2 imprinting system. International Journal of Oncology, 47, 1881-1889. https://doi.org/10.3892/ijo.2015.3181
MLA
Pan, Y., He, B., Chen, J., Sun, H., Deng, Q., Wang, F., Ying, H., Liu, X., Lin, K., Peng, H., Xie, H., Wang, S."Gene therapy for colorectal cancer by adenovirus-mediated siRNA targeting CD147 based on loss of the IGF2 imprinting system". International Journal of Oncology 47.5 (2015): 1881-1889.
Chicago
Pan, Y., He, B., Chen, J., Sun, H., Deng, Q., Wang, F., Ying, H., Liu, X., Lin, K., Peng, H., Xie, H., Wang, S."Gene therapy for colorectal cancer by adenovirus-mediated siRNA targeting CD147 based on loss of the IGF2 imprinting system". International Journal of Oncology 47, no. 5 (2015): 1881-1889. https://doi.org/10.3892/ijo.2015.3181