Pharmacologic suppression of JAK1/2 by JAK1/2 inhibitor AZD1480 potently inhibits IL-6-induced experimental prostate cancer metastases formation

摘要: Metastatic prostate cancer is lethal and lacks effective strategies for prevention or treatment, requiring novel therapeutic approaches. Interleukin-6 (IL-6) a cytokine that has been linked with pathogenesis by multiple studies. However, the direct functional roles of IL-6 in growth progression have unclear. In present study, we show produced distant metastases clinical cancers. IL-6-activated signaling pathways cells induced robust 7-fold increase formation nude mice. We further promoted migratory cell phenotype, including increased migration, microtubule reorganization, heterotypic adhesion to endothelial cells. IL-6-driven metastasis was predominantly mediated Stat3 lesser extent ERK1/2. Most importantly, pharmacologic inhibition Jak1/2 AZD1480 suppressed IL-6-induced signaling, phenotypes, metastatic dissemination vivo conclusion, demonstrate directly promotes vitro via Jak-Stat3 pathway, can be effectively targeting using inhibitor AZD1480. Our results therefore provide strong rationale development inhibitors as therapy cancer.