Department of General Surgery, Affiliated People's Hospital, Shanghai, PR, China.
Neoplasma. 2011;58(5):396-405. doi: 10.4149/neo_2011_05_396.
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.
异常信号转导子和转录激活因子 3（STAT3）信号通路是肿瘤侵袭和转移的主要原因；然而，其潜在机制尚不清楚。上皮-间充质转化（EMT）是上皮来源的癌症侵袭过程中早期发生的事件。STAT3 信号通路是否参与 EMT 仍然难以确定。本研究旨在评估阻断 STAT3 信号通路对白细胞介素 6（IL-6）诱导人胰腺癌细胞 EMT 的影响。我们使用 SW1990 细胞，并通过将这些细胞暴露于可溶性因子白细胞介素 6（IL-6）来诱导它们发生 EMT。通过逆转录-PCR、实时 PCR 和 Western blot 检测 Snail、E-钙黏蛋白和 Twist 的表达。在倒置相差显微镜下观察细胞形态。通过体外细胞侵袭实验测定细胞侵袭能力。我们的结果表明，STAT3 信号通路参与了胰腺癌细胞的侵袭和 EMT，而 IL-6 诱导的 EMT 与 STAT3 信号通路的激活有关。用 RNAi 沉默 STAT3 基因抑制 STAT3 信号通路激活，抑制胰腺癌细胞的 EMT。总之，STAT3 信号通路通过调节 Snail 基因表达在胰腺癌 EMT 过程中发挥重要作用。更好地了解 STAT3 信号通路在 EMT 中的作用可能有助于开发胰腺癌侵袭和转移的新治疗策略。
