Targeting receptor for advanced glycation end products (RAGE) expression induces apoptosis and inhibits prostate tumor growth.
Expression of receptor for advanced glycation end products (RAGE) plays a key role in the progression of prostate cancer. However, the therapeutic potential of targeting RAGE expression in prostate cancer is not yet evaluated. Therefore in this study, we have investigated the effects of silencing the expression of RAGE by RNAi approach both in vitro and in vivo. The results of this study showed that down regulation of RAGE expression by RNAi inhibited the cell proliferation of androgen-dependent (LNCaP) and androgen-independent (DU-145) prostate cancer cells. Furthermore, targeting RAGE expression resulted in apoptotic elimination of these prostate cancer cells by activation of caspase-8 and caspase-3 death signaling. Of note, the levels of prostate specific antigen (PSA) were also reduced in LNCaP cells transfected with RAGE RNAi constructs. Importantly, the RAGE RNAi constructs when administered in nude mice bearing prostate tumors, inhibited the tumor growth by targeting the expression of RAGE, and its physiological ligand, HMGB1 and by up regulating death receptors DR4 and DR5 expression. Collectively, the results of this study for the first time show that targeting RAGE by RNAi may be a promising alternative therapeutic strategy for treating prostate cancer.
Department of Biomedical Sciences, University of Illinois, College of Medicine, Rockford, IL 61107, USA.
Indira
I
Elangovan
Sivasakthivel
S
Thirugnanam
Aoshuang
A
Chen
Guoxing
G
Zheng
Maarten C
MC
Bosland
André
A
Kajdacsy-Balla
Munirathinam
M
Gnanasekar
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D024243:HMGB1 Protein; D008024:Ligands; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; D020169:Caspases