Interleukin-6 Promotes Cervical Cancer Development Through Janus Kinase 2/Signal Transducer and Activator of Transcription 6 Signaling Pathway

Abstract

Interleukin (IL)-6 regulates several cellular processes such as proliferation, differentiation and immune regulation. The pathogenesis of cervical cancer is closely related to abnormal secretion and regulation of cytokines. IL-6 in the pathogenesis of cervical cancer was investigated in the present study. In our work, we collected cervical cancer tissues and adjacent normal tissues first and then established mouse model of cervical cancer for following assays. Immunohistochemistry and Western blot analysis were performed to detect IL-6, JAK3 and STAT6 and qRT-PCR determined VEGF, MMP-2, MMP-9 and others in adjacent tissues and cancer tissues. MTT was used to detect the capability of proliferation, invasion and migration. Chromatin immunoprecipitation was employed to verify the binding of STAT6 to IL-6. The effect of STAT6 inhibitors, AS1517499 on JAK3/STAT6 axis was also detected through in vivo experiments. Except IL-6, the related proteins were upregulated in cervical cancer tissues. IL-6 (25–100 ng/mL) accelerated the growth of Hela cells. IL-6 improved cell migratory and invasive ability when recombinant IL-6 promoted phosphory-lation and JAK3/STAT6. The activity of IL-6 in Hela was mediated by JAK3/STAT6 signaling pathway as AS1517499 inhibited IL-6-induced JAK3/STAT6 phosphorylation and STAT6 bound to the IL-6 promoter. STAT6 inhibitors significantly suppressed tumor growth and reduced p-STAT3 level. IL-6 contributes to cervical cancer through JAK3/STAT6 signaling which could be a cornerstone of subsequent anti-cervical cancer treatment.