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目的 观察JAK2激酶抑制剂AG4 90对胃癌细胞侵袭以及对基质金属蛋白酶类(MMPs)、组织型基质金属蛋白酶抑制物 (TIMPs)表达的影响 ,探讨STAT3信号转导通路在胃癌侵袭转移调控中的作用。方法 应用JAK2激酶抑制剂AG4 90处理胃癌BGC 82 3细胞 ,Matrigel肿瘤体外侵袭模型检测肿瘤细胞侵袭 ;Westernblot检测STAT3、MMP 2、MMP 9蛋白表达及活性 ;RT PCR检测MMPs、TIMPsmRNA的表达。结果 AG4 90可抑制JAK2 /STAT3信号转导通路活化及胃癌BGC 82 3细胞侵袭 ,在此过程中AG4 90在mRNA和蛋白水平抑制MMP 2和MMP 9表达 ,同时上调TIMP 1、TIMP 2mRNA的表达。结论 STAT3信号转导通路参与胃癌细胞侵袭调控 ,阻断STAT3通路活化可以抑制胃癌细胞侵袭 ,这一作用可能是通过抑制MMP 2和MMP 9表达以及上调TIMP 1和TIMP 2表达实现的。
Objective To investigate the effect of JAK2 kinase inhibitor AG4 90 on the invasion of gastric cancer cells and the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase (TIMPs) and the role of STAT3 signal transduction pathway in the regulation of invasion and metastasis of gastric cancer . Methods The gastric cancer cell line BGC-82 3 was treated with JAK2 kinase inhibitor AG4 90. The invasion of tumor cells was detected by Matrigel invasion in vitro. The protein expressions of STAT3, MMP 2 and MMP 9 were detected by Western blot. The expressions of MMPs and TIMP mRNA were detected by RT-PCR. Results AG4 90 inhibited the activation of JAK2 / STAT3 signal transduction pathway and invasion of gastric cancer cell line BGC-82 3. In the process, AG4 90 inhibited the expression of MMP 2 and MMP 9 at the mRNA and protein levels and up-regulated the expressions of TIMP-1 and TIMP-2 mRNA. Conclusion The STAT3 signal transduction pathway is involved in the invasion and metastasis of gastric cancer cells. Blocking the activation of STAT3 pathway can inhibit the invasion of gastric cancer cells. This effect may be through inhibiting the expression of MMP2 and MMP9 and up-regulating the expressions of TIMP-1 and TIMP-2.