The androgen receptor (AR) plays a pivotal role in prostate cancer, making it a potential therapeutic target. Short-hairpin RNA (shRNA) inhibits gene expression and offers a novel strategy to eradicate disease. Ultrasound-mediated gene transfection is a promising gene delivery method. This study sought to determine whether targeting silencing androgen receptor gene by shRNA with low-intensity focused ultrasonic irradiation could be used as effective therapy for prostate cancers in vivo. A plasmid-based short-hairpin RNA combined with low-intensity focused ultrasonic irradiation approach was used to specifically knock down the expression of AR in prostate cancer 22RV1 cells in vivo. The growth of 22RV1 tumors that had been subcutaneously xenografted was evaluated and expression level of AR was determined by immunohistochemical staining. The proliferative index (PI) and the apoptotic index (AI) were respectively derived from the percentage of positive cells by Ki-67 immunohistochemical staining and TUNEL assay. The plasmid-based AR shRNA administrated intravenously significantly inhibited the tumor growth and AR expression. These inhibitory effects of AR shRNA were augmented when the region of tumor received low-intensity focused ultrasound irradiation. Immunohistochemical staining and TUNEL assay confirmed AR shRNA with low-intensity focused ultrasonic irradiation exhibited growth-inhibitory, antiproliferative, and apoptotic effects on prostate cancer xenografts. The authors showed for the first time that the knockdown of AR expression by plasmid-based AR shRNA with low-intensity focused ultrasonic irradiation significantly suppressed the tumor growth of prostate cancer in vivo.
Keywords: Prostate cancer; androgen receptor; focused ultrasound; gene silencing.
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