JAK2激酶抑制剂AG490对结肠癌HT-29细胞侵袭性的影响

目的观察JAK2激酶抑制剂AG490对结肠癌HT-29细胞侵袭以及对基质金属蛋白酶-2（MMP-2）表达的影响，探讨STAT3信号转导通路在结肠癌侵袭转移调控中的作用。方法应用JAK2激酶抑制剂AG490处理结肠癌HT-29细胞，Matrigel肿瘤体外侵袭模型检测肿瘤细胞侵袭；Western blot检测STAT3蛋白表达；逆转录-聚合酶链反应（RT—PCR）检测MMP2mRNA表达。结果AG490可抑制JAK2／STAT3信号转导通路活化及结肠癌HT-29细胞侵袭，在此过程中AG490在mRNA水平抑制MMP-2表达。结论STAT3信号转导通路参与结肠癌细胞侵袭调控，阻断STAT3通路活化可抑制结肠癌细胞侵袭，这一作用可能是通过抑制MMP-2表达实现的。

Effect of AG490 on invasiveness of HT-29 cells

Objective To investigate the role of STAT3 signaling pathway in colorectal cancer invasiveness. Methods Janus kinase 2 selective inhibitor AG490 was used to inhibit the activation of STAT3 signaling pathway. Matrigel-coated transwell was employed to estimate the invasiveness of HT-29 cells. The changes in the activity of STAT3 and the expression of MMP-2 were measured by Western blot and RT-PCR respectively. Results The activation of STAT3 signaling pathway was suppressed by AG490, and at the same time, AG490 significantly decreased the invasiveness of colorectal cancer cell HT- 29 through Matrigel-coated filters. Decreased invasiveness was associated with the inhibition of MMP-2 at mRNA level. Conclusion Invasiveness of colorectal cancer cells may be suppressed by inhibition of STAT3 signaling pathway through down-regulating MMP-2.