Cypermethrin inhibits interleukin-6-induced androgen receptor transactivation through signal transducer and activator of transcription 3

Abstract

The insecticide cypermethrin has been considered as an endocrine-disrupting chemicals (EDCs) with anti-androgenic activity by interfering with interleukin-6 (IL-6) – induced ligand-independent AR signaling. The purpose of this study was to clarify whether the signal transducer and activator of transcription 3 (STAT3) was involved in the antagonism effect of cypermethrin. In this study, the Western blot was to test the level of STAT3 phosphorylation and the mammalian two-hybrid assay was developed to assess the AR–STAT3 interaction. The date showed that IL-6 increased the phosphorylation level of STAT3 and enhanced the AR–STAT3 interaction. Cypermethrin did not affect the phosphorylation level of STAT3 induced by IL-6, while suppressed the AR-STAT3 interaction induced by IL-6 significantly at the concentration of 10−5 M (p < 0.05). The study indicates cypermethrin inhibits IL-6–induced AR signaling by suppressing the interaction between the AR and STAT3. We provide a novel mechanism of cypermethrin-mediated antagonism on IL-6–induced AR activation associated with STAT3.