title: Suppression of Bcl-xL expression by a novel tumor-specific RNA interference system inhibits proliferation and enhances radiosensitivity in prostatic carcinoma cells.
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.
authors.affiliation: Research Center, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, 710038 Xi'an, Shaanxi Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Ke
authors.initials: K
authors.lastname: Dong
authors.forename: San-Hua
authors.initials: SH
authors.lastname: Wei
authors.forename: Shi-Yin
authors.initials: SY
authors.lastname: Cheng
authors.forename: Hui-Zhong
authors.initials: HZ
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D020287:In Situ Nick-End Labeling; D008156:Luciferases / Q000235:genetics; D008297:Male; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference / Q000502:physiology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D014183:Transplantation, Heterologous; D014410:Tumor Stem Cell Assay; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D011838:Radiation-Sensitizing Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D051020:bcl-X Protein; D049452:Green Fluorescent Proteins; D008156:Luciferases; C022616:thiazolyl blue