Interleukin-11 induces the expression of matrix metalloproteinase 13 in gastric cancer SCH cells partly via the PI3K-AKT and JAK-STAT3 pathways

Interleukin (IL)-11 is expressed in the majority of gastric carcinomas and has been associated with an aggressive phenotype and poor prognosis of gastric adenocarcinoma. Matrix metalloproteinase (MMP)-13 has been detected in numerous invasive malignant tumor types and exhibits a broad spectrum of activities on connective tissue components. In this study, we investigated whether IL-11 affects the expression of MMP-13 in human gastric cancer cells, as well as the underlying mechanism. Using western blot assays, we investigated the effect of recombinant human (rh) IL-11 on the expression of MMP-13 in gastric carcinoma cell lines. Using the PI3K inhibitor wortmannin and RNA interference to target the STAT3 gene, we investigated the effects of PI3K inhibition and/or STAT3 depletion on the expression of the MMP-13 protein. Results showed that IL-11 induced MMP-13 expression in a time- and concentration-dependent manner in SCH cells. IL-11 activated PI3K-AKT and JAK-STAT3 signal transduction. Wortmannin and depletion of STAT3 by means of small interfering RNA (siRNA) synergistically reduced the expression of MMP-13. These findings suggested that IL-11 induces the expression of MMP-13 in gastric cancer SCH cells partly via the PI3K-AKT and JAK-STAT3 pathways.