Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells

  • Authors:
    • Qifang Long
    • Ru Yang
    • Weixian Lu
    • Weipei Zhu
    • Jundong Zhou
    • Cui Zheng
    • Dongmei Zhou
    • Ling Yu
    • Jinchang Wu
  • View Affiliations

  • Published online on: November 21, 2016     https://doi.org/10.3892/or.2016.5263
  • Pages: 155-162
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Abstract

Cancer stem cells are a small subset of cancer cells that contribute to cancer progression, metastasis, chemoresistance and recurrence. CD133-positive (CD133+) ovarian cancer cells have been identified as ovarian cancer stem cells. Adenovirus-mediated gene therapy is an innovative therapeutic method for cancer treatment. In the present study, we aimed to develop a new gene therapy to specifically eliminate CD133+ ovarian cancer stem cells by targeting CD133. We used the Cre/LoxP system to augment the selective expression of the truncated Bid (tBid) gene as suicide gene therapy in CD133+ ovarian cancer stem cells. The adenovirus (Ad)-CD133-Cre expressing Cre recombinase under the control of the CD133 promoter and Ad-CMV-LoxP-Neo-LoxP-tBid expressing tBid under the control of the CMV promoter were successfully constructed using the Cre/LoxP switching system. The co-infection of Ad-CMV-LoxP-Neo-LoxP-tBid and Ad-CD133-Cre selectively induced tBid overexpression, which inhibited cell growth and triggered the cell apoptosis of CD133+ ovarian cancer stem cells. The Cre/LoxP system-mediated tBid overexpression activated the pro-apoptotic signaling pathway and augmented the cytotoxic effect of cisplatin in CD133+ ovarian cancer stem cells. Furthermore, in xenograft experiments, co-infection with the two recombinant adenoviruses markedly suppressed tumor growth in vivo and promoted cell apoptosis in tumor tissues. Taken together, the present study provides evidence that the adenovirus-mediated tBid overexpression induced by the Cre/LoxP system can effectively eliminate CD133+ ovarian cancer stem cells, representing a novel therapeutic strategy for the treatment of ovarian cancer.
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January-2017
Volume 37 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Long Q, Yang R, Lu W, Zhu W, Zhou J, Zheng C, Zhou D, Yu L and Wu J: Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells. Oncol Rep 37: 155-162, 2017
APA
Long, Q., Yang, R., Lu, W., Zhu, W., Zhou, J., Zheng, C. ... Wu, J. (2017). Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells. Oncology Reports, 37, 155-162. https://doi.org/10.3892/or.2016.5263
MLA
Long, Q., Yang, R., Lu, W., Zhu, W., Zhou, J., Zheng, C., Zhou, D., Yu, L., Wu, J."Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells". Oncology Reports 37.1 (2017): 155-162.
Chicago
Long, Q., Yang, R., Lu, W., Zhu, W., Zhou, J., Zheng, C., Zhou, D., Yu, L., Wu, J."Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells". Oncology Reports 37, no. 1 (2017): 155-162. https://doi.org/10.3892/or.2016.5263