Dysregulation of Apoptosis Involves the Extrinsic Pathway in Human Prostate Cancer

OBJECTIVE: Apoptosis or programmed cell death is a key regulator of physiological growth control and regulation of tissue homeostasis. Transformation and malignant progression of prostate cancer (CaP) is due to a failure to regulate the apoptosis of prostatic epithelial cells. To investigate the expression of apoptotic proteins in patients with CaP and benign prostatic hyperplasia (BPH), we respectively examined Bcl-2, caspase-9, caspase-8 and cleaved caspase-3 to further determine the intrinsic or extrinsic apoptotic pathway. MATERIALS AND METHODS: The study group consisted of 18 patients with CaP who underwent a radical prostatectomy. The control group consisted of 36 patients with BPH who underwent transurethral resection of the prostate (TURP). Tissue samples were respectively acquired from the gross tumor site and from resected chips. We detected the expression of apoptotic proteins by immunoblotting and immunohistochemical staining. Data were analyzed using Student's t-test. RESULTS: There was no statistically significant difference in the expression of Bcl-2 or caspase-9 in the 2 groups. But statistical decreases in the expressions of caspase-8 and cleaved caspase-3 in the CaP group compared to the BPH group were respectively demonstrated by Western blotting and immunohistochemical staining. This study demonstrated the downregulation of caspase-8 and cleaved caspase-3 expressions in the CaP group. CONCLUSIONS: The present study shows that the dysregulation of apoptosis involved the extrinsic pathway in patients with CaP. Inducing caspase-8 or caspase-3 activation may be a novel treatment for CaP. A greater understanding of the molecular mechanisms of tumor cell apoptosis may enable better therapeutic design and prevention of CaP.