STAT3 signaling pathway mediates cyclooxygenase-2 selective inhibitory-induced apoptosis and inhibited proliferationIn of vascular smooth muscle cells

Objective:To investigate the relationship between STAT3 signal transduction pathway and the mechanism of selective cyclooxygenase-2 inhibitor -NS-398 action against vascular smooth muscle cells(VSMCs). Revealing the potential mechanism of NS-398 effect on VSMCs. Method:VSMCs of rat were treated with NS-398(a selective COX-2 inhibitor). MTT assay and flow cytometry were used to measure the proliferation and apoptosis. RT-PCR was performed on detecting the levels of COX-2 mRNA expression from VSMCs. The expression of STAT3, p-STAT3, JAK2, P-JAK2, Cyclin D1 and Bcl-2 proteins was measured by Western blot. Result:High expression of COX-2 mRNA was detected VSMC and there was obvious decline of COX-2 mRNA after NS-398 treating(P0.01). NS-398 inhibited the cells proliferation and induced apoptosis in a dose、time-dependent manner and resulted in significant downregulation of STAT3, p-STAT3, JAK2, P-JAK2, Cyclin D1,Bcl-2(P0.01). Conclusion:Selective COX-2 inhibitor NS-398 may inhibit the proliferation and induce apoptosis of VSMCs through decreasing expression of COX-2 mRNA. STAT3 Signaling pathway mediates COX-2-selective inhibitor-induced apoptosis and proliferative inhibition in VSMCs,which may be a new target of selective COX-2 inhibitor effect on VSMCs.