RNA interference targeting mutant p53 inhibits growth and induces apoptosis in DU145 human prostate cancer cells.
p53 is the most frequently mutated tumor suppressor gene in human cancer. Recent studies have indicated that p53 mutants not only lose tumor suppression activity but also gain novel oncogenic functions that contribute to tumor malignancy. In this study, we explored mutant p53 as a target for novel anti-cancer treatment in prostate cancer. Using the DU145 human androgen-independent prostate cancer cell line, we show that silencing of mutant p53 gene by RNA interference led to significant inhibition of cell viability and growth, which was associated with cell cycle arrest at G1 and G2/M phase, and ultimately induced massive apoptosis. Mechanistically, p53-siRNA inhibited phosphatidylinositol 3'-kinase/Akt signaling pathway, which might be responsible for the reduced proliferation and apoptosis induction. These findings suggest that RNA interference targeting mutant p53 may serve as a novel therapeutic strategy for the treatment of androgen-independent prostate cancer.
Zhu
HaiBin
H
Department of Gynecology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Mao
Qiqi
Q
Lin
Yiwei
Y
Yang
Kai
K
Xie
Liping
L
D017209:Apoptosis / Q000235:genetics*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D055785:Gene Knockdown Techniques; D018390:Gene Targeting / Q000379:methods*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D050505:Mutant Proteins / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D050505:Mutant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53