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

• Published in: Cancer chemotherapy and pharmacology 2008-05, Vol.61 (6), p.943-952
• Main Authors: Wang, Rui, Lin, Fang, Wang, Xi, Gao, Ping, Dong, Ke, Wei, San-Hua, Cheng, Shi-Yin, Zhang, Hui-Zhong
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Apoptosis - drug effects; bcl-X Protein - antagonists & inhibitors; bcl-X Protein - biosynthesis; bcl-X Protein - genetics; Biological and medical sciences; Blotting, Western; Cancer Research; Cell Line, Tumor; Cell Proliferation - drug effects; Down-Regulation - drug effects; Flow Cytometry; Green Fluorescent Proteins - genetics; Humans; In Situ Nick-End Labeling; Luciferases - genetics; Male; Medical sciences; Medicine; Medicine & Public Health; Neoplasm Transplantation; Nephrology. Urinary tract diseases; Oncology; Original Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Plasmids - genetics; Promoter Regions, Genetic - genetics; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Radiation-Sensitizing Agents - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference - physiology; Tetrazolium Salts; Thiazoles; Transfection; Transplantation, Heterologous; Tumor Stem Cell Assay; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-007-0548-y

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.