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

Autor: Rui Wang, Fang Lin, Xi Wang, Ping Gao, Ke Dong, San-Hua Wei, Shi-Yin Cheng, Hui-Zhong Zhang
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Zdroj: Cancer Chemotherapy & Pharmacology; May2008, Vol. 61 Issue 6, p943-952, 10p, 2 Black and White Photographs, 1 Diagram, 2 Charts, 8 Graphs
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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