Naftopidil, a selective α1 adrenoceptor antagonist, inhibits the growth of lung fibroblasts and attenuates bleomycin-induced lung fibrosis in mice

Abstract

Introduction: Naftopidil, a selective α1 adrenoceptor antagonist, inhibits the growth of prostate fibroblasts by inducing cell apoptosis without the blocking effects of α1 adrenoceptor. However, the effects of naftopidil are little known on the growth of lung fibroblast and lung fibrosis. Methods: We examined the effects of naftopidil on the growth of lung fibroblasts using 5-Bromo-29-deoxyuridine (BrdU) incorporation assay. We also examined whether naftopidil induced the apoptosis of lung fibroblasts by analyzing the levels of cleaved caspase-3 by Western blotting. The effects of naftopidil on bleomycin-induced lung fibrosis in mice were examined. Results: Naftopidil inhibited the growth of lung fibroblasts in a dose-dependent manner. This inhibitory effect was weakened in lung fibroblast derived from a patient with idiopathic pulmonary fibrosis in comparison to normal human lung fibroblasts. Western blotting revealed that naftopidil induced the apoptosis of lung fibroblasts similarly to prostate fibroblasts. Naftopidil also attenuated bleomycin-induced lung fibrosis in mice. Conclusions: Naftopidil, a selective α1 adrenoceptor antagonist, inhibits the growth of lung fibroblasts by inducing cell apoptosis and attenuates bleomycin-induced lung fibrosis in mice.