JAK2/STAT3信号通路在胃癌发病机制中的作用及AG490干预研究

Study on effect of JAK2/STAT3 signal pathway on pathogenesis of gastric cancer and intervention effect of AG490

目的以重组人白介素-2(IL-2)作用于胃癌细胞系AGS,观察其对胃癌细胞生长增殖的影响;利用蛋白质酪氨酸激酶2(JAK2)特异性抑制剂AG490阻断JAK2/STAT3(信号传导子与激活子3)的异常激活,研究JAK2/STAT3信号传导通路在胃癌发病中的作用。方法以重组人IL-2干预、四唑鎓盐(XTT)法检测胃癌细胞系AGS增殖活性;以特异性抑制剂AG490抑制JAK通路,XTT法检测细胞增殖活性,并检测干预前后JAK蛋白、STAT3蛋白、p-STAT3蛋白表达水平。结果重组人IL-2可呈浓度依赖性抑制AGS细胞增殖,JAK特异性抑制剂AG490可呈浓度依赖性抑制AGS细胞增殖,各组间比较,差异有统计学意义(P<0.05),AG490可显著抑制JAK2、STAT3、p-STAT3蛋白表达。结论 JAK2-STAT3信号传导通路可能参与了早期胃癌的生物学行为。

Objective To investigate the effect of recombinant human interleukin-2 （rhIL-2）on the growth of gastric car- cinoma cell line AGS, and to study the role of JAK-STAT3 signal transduction pathway in the development of gastric cancer by us- ing the JAK specific inhibitor AG490 to block the abnormal activation of JAK2/STAT3. Methods Gastric carcinoma cell line AGS was cultured,rhIL-2 was added to the culture system, the proliferation activity was analyzed by XTI＂ method. AG490 as the specific inhibitor of JAK was added to the cell culture medium,the proliferation activity was also analyzed by xTr method, and Western blotting was used to determine the expression level of JAK protein, STAT3 protein and p-STAT3. Results RhIL-2 could inhibit the AGS cell proliferation in a concentration depended manner;AG490 as the specific inhibitor of JAK could inhibit the AGS cell proliferation in a concentration depended manner;G490 could significantly inhibit the expression of JAK protein, STAT3 protein and p-STAT3. Conclusion JAK2-STAT3 signal transduction pathway participates in the biological behaviour of early gastric cancer.