Suppression of Bcl-xL expression by a novel tumor-specific RNA interference system inhibits proliferation and enhances radiosensitivity in prostatic carcinoma cells.
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.
Wang
Rui
R
Research Center, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, 710038 Xi'an, Shaanxi Province, China.
Lin
Fang
F
Wang
Xi
X
Gao
Ping
P
Dong
Ke
K
Wei
San-Hua
SH
Cheng
Shi-Yin
SY
Zhang
Hui-Zhong
HZ
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
D011838:Radiation-Sensitizing Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D051020:bcl-X Protein; D049452:Green Fluorescent Proteins; D008156:Luciferases; C022616:thiazolyl blue