Tong Qiangsong, Zhao Jun, Chen Zhaohui, Zeng Fuqing, Lu Gongcheng
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Chin Med J (Engl). 2003 Oct;116(10):1515-8.
To study the possibility of gene therapy for prostate cancer by blocking androgen receptor (AR) gene expression using a specific hammerhead ribozyme (RZ).
The hammerhead ribozyme expression vector pcDNA-hAR-RZ, specific to AR mRNA, was constructed and transfected into the prostate cancer cell line LNCaP by using lipofectamine. Androgen receptor expression was measured by RT-PCR and immunohistochemical methods. Cellular proliferation activities were assayed using the tetrazolium bromide colorimetry method; cell cycle changes were observed by flow cytometry; and cell apoptosis was detected by the TdT-mediated dUTP-biotin nick end labeling method.
One to seven days after transfection with the ribozyme expression vector, AR mRNA expression at molecular and protein levels in LNCaP cells decreased by 32.6% - 40.7% (P < 0.05) and 21.0% - 87.64% (P < 0.05) respectively, and cell proliferation was inhibited by 18.28% - 35.34% (P < 0.05). Meanwhile, the cell cycle was arrested at the G2/M stage, and apoptotic morphological changes occurred with an apoptosis rate of 25.17% (P < 0.01).
Ribozyme specific against AR mRNA is capable of inhibiting the expression AR and inducing the apoptosis in prostate cancer cells.
