Reduction of prostate cancer incidence by naftopidil, an α1-adrenoceptor antagonist and transforming growth factor-β signaling inhibitor

Objectives Quinazoline-based α1-adrenoceptor antagonists are known to inhibit prostate tumor growth through induction of apoptosis. We investigated the effect of a naphthalene-based α1-adrenoceptor antagonist, naftopidil, on prostate cancer incidence, apoptosis of prostatic cell and transforming growth factor-β signaling. Methods Prescription records were linked to pathological data for men who continued naftopidil (n = 766) or tamsulosin (n = 1015) for 3 months or longer between 2003 and 2010. Prostate cancer incidence was analyzed by log–rank test and the Cox proportional hazards model. Apoptosis and cell cycle arrest in human tissues were assessed by immunohistochemical detection of Bcl2 and p21, respectively. Growth inhibition and apoptosis treatment with naftopidil and tamsulosin were assessed in cancer cell lines. Interference with transforming growth factor-β signaling was examined by western blot analysis. Results Prostate cancer incidence was significantly lower in men who received naftopidil for 3 months or longer compared with tamsulosin (P = 0.035). Multivariate analysis confirmed a decreased hazard ratio, 0.46, for naftopidil use (P = 0.013), which was more evident with longer treatment. Immunohistochemical positivity for Bcl2, a marker for resistance to apoptosis, was less frequently detected in prostate cancer cells of men who received naftopidil compared with tamsulosin (P