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.

Keywords:

• Cypermethrin
• anti-androgen
• androgen receptor
• signal transducer and activator of transcription 3
• interleukin-6

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was financially supported by National Natural Science Foundation of China (No. 81273103), National Natural Science Foundation of China (No. 81461138036) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).