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Suppression of Bcl-xL expression by a novel tumor-specific RNA interference system inhibits proliferation and enhances radiosensitivity in prostatic carcinoma cells

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Abstract

Bcl-xL, a novel member of anti-apoptotic Bcl-2 family that play important roles in regulating cell survival and apoptosis, is frequently overexpressed in various kinds of human cancers, including prostatic carcinoma. To explore its possibility as a therapeutic target for prostatic carcinoma, we developed a novel tumor-specific RNA interference system by using survivin promoter and employed it to suppress exogenous reporters (LUC and EGFP) and endogenous gene Bcl-xL expression and analyzed its phenotypes. We found that expression of exogenous reporters (LUC and EGFP) was specifically inhibited in tumor cells but not in normal cells. We also observed that the specific inhibition of Bcl-xL in human prostatic carcinoma cells (PC3) strongly suppressed in vitro cell proliferation and in vivo tumorigenicity. We observed significant apoptosis induction and radiosensitivity enhancement in PC3 cells by the RNA interference-mediated suppression of Bcl-xL expression. All these results indicate that inhibition of Bcl-xL expression can result in potent antitumor activity and radiosensitization in human prostatic carcinoma.

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Acknowledgments

This study was supported by grants from National Natural Science Foundation of China (30371145) and Natural Science Foundation of Shaanxi Province (2003K10G44). We thank every one of department of clinical laboratory in Tangdu hospital, Fourth military medicine university for their sincere help and technical support.

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Authors and Affiliations

  1. Research Center, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, 710038, Xi’an, Shaanxi Province, China

    Rui Wang, Fang Lin, Xi Wang, Ping Gao, Shi-Yin Cheng & Hui-Zhong Zhang

  2. Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi’an, China

    Ke Dong & San-Hua Wei

Authors
  1. Rui Wang
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  2. Fang Lin
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  3. Xi Wang
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  4. Ping Gao
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  5. Ke Dong
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  6. San-Hua Wei
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  7. Shi-Yin Cheng
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  8. Hui-Zhong Zhang
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Correspondence to Hui-Zhong Zhang.

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Wang, R., Lin, F., Wang, X. et al. Suppression of Bcl-xL expression by a novel tumor-specific RNA interference system inhibits proliferation and enhances radiosensitivity in prostatic carcinoma cells. Cancer Chemother Pharmacol 61, 943–952 (2008). https://doi.org/10.1007/s00280-007-0548-y

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  • DOI: https://doi.org/10.1007/s00280-007-0548-y

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