The effects and mechanisms of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells in vitro

Aberrant Signal transducers and activators of transcription-3 (STAT3) signaling pathway is a major cause of tumor invasion and metastasis; the underlying mechanisms, however, are not well understood. Epithelial-mesenchymal transition (EMT) is an early event that occurs during invasion of cancers of an epithelial origin. It remains elusive whether STAT3signaling pathway is involved in EMT. The objective of this study was to evaluate the effect of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells. We used SW1990 cells and induced them to undergo EMT by exposing these cells to soluble factor interleukin-6 (IL-6). The expression of Snail, E-cadherin, and Twist was detected by reverse transcription-PCR, real-time PCR, and Western blotting. Cell morphology was observed under invert phase-contrast microscope. The invasion ability was determined by cell invasion assay in vitro. Our results demonstrated that STAT3 signaling pathway was involved in pancreatic cancer cell invasion and EMT, and that EMT induced by IL-6 was associated with the activation of STAT3 signaling pathway. Inhibition of STAT3 signaling pathway by silencing of the STAT3 gene with RNAi blocked STAT3 signaling pathway activation and suppressed EMT in pancreatic cancer cells. Collectively, the STAT3 signaling pathway plays an important role in the process of EMT of pancreatic cancer by regulating Snail gene expression. Better understanding of STAT3 signaling pathways in EMT may contribute to development of novel therapeutic strategies in invasion and metastasis of pancreatic cancer.