Janus kinase inhibitor AG490 inhibits gastric cancer cell invasiveness by down-regulation of MMPs and up-regulation of TIMPs / 中国普通外科杂志

ABSTRACT

Objective This study was to investigate the role of STAT3 signaling pathway in gastric 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 BGG-823 cells. Alterations in the activity of STAT3 and expression of MMPs and TIMPs were measured by Western blot and RT-PCR. Results The activation of STAT3 signaling pathway was suppressed by AG490. AC490 significantly decreased the invasiveness of gastric cancer cell line BGC-823 through Matrigel-coated filters. Decreased invasion was associated with the inhibition of MMP-2, and MMP-9 at both mRNA and protein levels by RT-PCR and Western blot. Meanwhile, the expression of TIMP-1, and TIMP-2 were up-regulated at mRNA levels. Conclusion Inhibition of STAT3 signaling pathway in AG490 suppresses gastric cancer cell invasiveness through down-regulation of several invasion-related factors including MMP-2, and MMP-9 and up-regulation of their inhibitors.