Up-regulation of MMP-10 expression is mediated by JAK2/STAT3 signaling pathway in human lung adenocarcinoma cell line

Objective To investigate the role of JAK2/STAT3 in the expression of MMP-10 in human lung adenocarcioma cell line and explore the molecular regulatory mechanism of MMP-10 expression.Methods A549 cells were seeded in six-well cell culture clusters,and were grown to 50%~70% confluence.0,12.5,25,50 ng/ml IL-6 and AG490+25 ng/ml IL-6 were given to A549 cells,respectively.The expression of JAK2,STAT3 and MMP-10 mRNA were detected with real-time RT-PCR assay.MMP-10 protein was determined by Western blot.Results In A549 cells,STAT3 mRNA levels at 25 ng/ml IL-6 was higher than at 0 ng/ml IL-6 (P0.05).50 μmol/L AG490,a specific JAK2 inhibitor,together with 25 ng/ml IL-6 decreased STAT3 mRNA expression by 36.73%,compared with 25 ng/ml IL-6(P0.01).On the contrary,MMP-10 mRNA levels in A549 cells treated with 50 μmol/L AG490+25 ng/ml IL-6 were significantly higher than with 25 ng/ml IL-6 (P0.01).MMP-10 protein levels at 12.5,25,50 ng/ml IL-6 were significantly increased compared with 0 ng/ml IL-6 (P0.05).50 μmol/L AG490,together with 25 ng/ml IL-6 reduced MMP-10 protein expression compared with 25 ng/ml IL-6 (P0.05).Conclusions It is suggested that the JAK2/STAT3 pathway might be involved in the expression of MMP-10 in A549 cells.