Effects of IL-6 and AG490 on regulation of Stat3 signaling pathway and invasion of human pancreatic cancer cells in vitro.
Effects of IL-6 and AG490 on regulation of Stat3 signaling pathway and invasion of human pancreatic cancer cells in vitro.
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DOI：
10.1186/1756-9966-29-51
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发表时间：
2010-05-19
期刊：
影响因子：
--
通讯作者：
Qiu Z
中科院分区：
文献类型：
--
作者：
Huang C;Yang G;Jiang T;Huang K;Cao J;Qiu Z
信号转导子和转录激活子3（Signaltransducerandactivatoroftranscription 3，Stat 3）是Janus-activatedkinase（Jak）/Stat 3信号通路的成员。Stat 3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关键作用。本研究旨在探讨Stat 3信号通路的激活和阻断机制及其对人胰腺癌细胞侵袭转移的影响。将Jak抑制剂AG 490和白细胞介素-6（IL-6）分别加入人胰腺癌细胞SW 1990和Capan-2的培养基中。通过MTT测定法测量细胞生长。采用Western blotting和免疫细胞化学方法检测磷酸化Stat 3（p-Stat 3）蛋白的表达，荧光定量PCR和Western blotting方法检测VEGF和MMP-2 mRNA和蛋白的表达。细胞侵袭实验检测SW 1990和Capan-2细胞的侵袭能力。Stat 3在Capan-2细胞中被IL-6激活，p-Stat 3在Capan-2细胞中的蛋白表达显著增加。IL-6能显著促进Capan-2细胞的生长（P < 0.05），并能显著提高VEGF和MMP-2的mRNA和蛋白表达。IL-6还能增强Capan-2细胞的侵袭能力。AG 490抑制SW 1990细胞中Stat 3的活化。Western blotting和免疫细胞化学分析显示，AG 490处理后SW 1990细胞中p-Stat 3蛋白表达明显降低。AG 490可显著抑制Capan-2细胞的生长（P < 0.05），并显著降低VEGF和MMP-2的mRNA和蛋白表达。AG 490可降低SW 1990细胞的侵袭能力。Stat 3的异常激活在胰腺癌的侵袭和转移中起重要作用。Stat 3信号通路的激活和阻断可影响胰腺癌细胞的侵袭能力和VEGF、MMP-2基因的表达。Stat 3信号通路可能为胰腺癌的治疗提供新的靶点。
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.
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