Inhibition of prostate cancer using RNA interference-directed knockdown of platelet-derived growth factor receptor - Abstract

Department of Urology, Seoul National University College of Medicine, Seoul, Korea.


To determine whether platelet-derived growth factor receptor (PDGFR) plays a role in the tumorigenicity of prostate cancer cells.

PC3 prostate cancer cells were transfected with small interfering (si)PDGFR-α and siPDGFR-β, constructed according to the conventional small interfering RNA design standard. Reverse transcriptase polymerase chain reaction, Western blot analysis, and cell growth were studied to determine the characteristics of PDGFR-α and PDGFR-β in vitro. The prostate cancer xenograft model was established to investigate whether knockout of PDGFR-α and PDGFR-β decreases prostate cancer tumor growth in vivo. The experimental groups were defined as group 1 (PC3 cells only), group 2 (PC3 cells transfected with small interfering green fluorescent protein), group 3 (PC3 cells transfected with siPDGFR-α), group 4 (PC3 cells transfected with siPDGFR-β), and group 5 (PC3 cells transfected with siPDGFR-α and siPDGFR-β).

Western blot analysis revealed that siPDGFR-α and siPDGFR-β significantly blocked PDGFR-α and PDGFR-β protein expression. After 48 hours of transfection of the PC3 cells with siPDGFR-α and siPDGFR-β, the relative fractions of viable cells were reduced to 47.7% (P = .007) and 38.5% (P = .010). In vivo, mice treated with siPDGFR-α or siPDGFR-β and siPDGFR-α plus siPDGFR-β had significant tumor cell growth arrest compared with the mice in groups 1 and 2 (P = .001). In addition, a significant reduction in the microvessel density was observed in tumors from the mice treated with siPDGFR-α or siPDGFR-β and siPDGFR-α plus siPDGFR-β (P < .001).

The results of the present study suggest that siPDGFR-α and siPDGFR-β might inhibit prostate cancer cell growth by the suppression of angiogenesis.

Written by:
Park YH, Seo SY, Ha M, Ku JH, Kim HH, Kwak C.   Are you the author?

Reference: Urology. 2011 Apr 8. Epub ahead of print.
doi: 10.1016/j.urology.2011.01.050

PubMed Abstract
PMID: 21481440 Prostate Cancer Section