Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai, PR China.
J Exp Clin Cancer Res. 2010 May 19;29(1):51. doi: 10.1186/1756-9966-29-51.
Signal transducer and activator of transcription 3 (Stat3) is a member of the Janus-activated kinase(Jak)/Stat signaling pathway. Abnormal activation of Stat3 plays a critical role in metastasis and invasion in varieties of human tumors including pancreatic cancer. This study aimed to investigate the mechanisms of activation and blocking of the Stat3 signaling pathway and its effects on invasion and metastasis of human pancreatic cancer cells.
The Jak inhibitor AG490 and interleukin-6 (IL-6) were added to the culture media of human pancreatic cancer cells SW1990 and Capan-2, respectively. Cell growth was measured by MTT assays. Western blotting and immunocytochemistry were performed to detect phosphorylated Stat3 (p-Stat3) protein, while VEGF and MMP-2 mRNA and protein expression were examined with fluorescence quantitative polymerase chain reaction and Western blotting, respectively. The invasion ability of SW1990 and Capan-2 cells was determined by cell invasion assay.
Stat3 was activated by IL-6 in Capan-2 cells; protein expression of p-Stat3 was increased significantly in Capan-2 cells. IL-6 remarkably promoted the growth of Capan-2 cells (P < 0.05), and VEGF and MMP-2 mRNA and protein expression were increased significantly. Also, IL-6 increased the invasion ability of Capan-2 cells. AG490 inhibited Stat3 activation in SW1990 cells. Western blotting and immunocytochemistry analysis showed that p-Stat3 protein expression was decreased significantly with AG490 treatment in SW1990 cells. AG490 remarkably inhibited the growth of Capan-2 cells (P < 0.05), and VEGF and MMP-2 mRNA and protein expression was decreased significantly. And AG490 decreased the invasion ability of SW1990 cells.
Abnormal activation of Stat3 plays an important role in the invasion and metastasis of pancreatic cancer. Activation and blocking of the Stat3 signaling pathway can affect invasion ability and expression of the VEGF and MMP-2 genes in pancreatic cancer cells. The Stat3 signaling pathway may provide a novel therapeutic target for treatment of pancreatic cancer.
信号转导子和转录激活子 3（Stat3）是 Janus 激活激酶（Jak）/Stat 信号通路的一个成员。Stat3 的异常激活在包括胰腺癌在内的多种人类肿瘤的转移和侵袭中起着关键作用。本研究旨在探讨 Stat3 信号通路的激活和阻断机制及其对人胰腺癌细胞侵袭和转移的影响。
将 Jak 抑制剂 AG490 和白细胞介素-6（IL-6）分别添加到人胰腺癌细胞 SW1990 和 Capan-2 的培养基中。通过 MTT 测定法测量细胞生长。通过 Western 印迹和免疫细胞化学检测磷酸化 Stat3（p-Stat3）蛋白，通过荧光定量聚合酶链反应和 Western 印迹分别检测 VEGF 和 MMP-2 mRNA 和蛋白表达。通过细胞侵袭试验测定 SW1990 和 Capan-2 细胞的侵袭能力。
IL-6 激活了 Capan-2 细胞中的 Stat3；Capan-2 细胞中 p-Stat3 蛋白表达显著增加。IL-6 显著促进 Capan-2 细胞的生长（P<0.05），并显著增加 VEGF 和 MMP-2 mRNA 和蛋白表达。此外，IL-6 增加了 Capan-2 细胞的侵袭能力。AG490 抑制了 SW1990 细胞中的 Stat3 激活。Western 印迹和免疫细胞化学分析显示，AG490 处理后 SW1990 细胞中 p-Stat3 蛋白表达显著降低。AG490 显著抑制 Capan-2 细胞的生长（P<0.05），并显著降低 VEGF 和 MMP-2 mRNA 和蛋白表达。AG490 降低了 SW1990 细胞的侵袭能力。
Stat3 的异常激活在胰腺癌的侵袭和转移中起着重要作用。Stat3 信号通路的激活和阻断可影响胰腺癌细胞中 VEGF 和 MMP-2 基因的侵袭能力和表达。Stat3 信号通路可能为胰腺癌的治疗提供新的治疗靶点。
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