Furthermore, recent studies demonstrate that JNK is frequently over e pressed in different cancer tissues, and up regulation of JNK may be closely associ ated with cancer invasion, however, whether JNK participates in regulation of IL 1B induced gastric cancer cell migration and invasion remains largely unknown. Gastric adenocarcinoma is the most common neo plastic tumor of the stomach. therefore, we focused on GA in this study. Here, we investigated the activation of p38 and JNK in response to IL 1B, and their effect on IL 1B induced metastatic potential of GA cells in vitro or vivo. Additionally, the e pression of phospho p38 in GA, its relationship to the clinicopathologic features of GA, and the correlation between the e pression of IL 1B and p p38 were investigated in human paraffin embedded GA tissues using immunohistochemistry.

Finally, Inhibitors,Modulators,Libraries we also characterized the molecular mechanisms which regulate the IL 1B induced p38 mediated meta static potential of GA cells. Results IL 1B induced activation of p38 promotes GA cell migration and invasion in vitro First, we investigated whether IL 1B was able to activate p38 signaling in GA cells. As shown in Figure 1, activation of p38 was detected in both GA cell lines after treatment with IL 1B for 30 min. IL 1B induced activation of p38 was inhibited by the p38 inhibitor SB202190. P38 can promote the migration and invasion of different Inhibitors,Modulators,Libraries cancer cells. To investigate whether IL 1B can promote the migration and invasion of GA cells via activating p38 signaling, GA cells transfected with a scrambled siRNA or p38 siRNA, or GA cells pre treated with or without the p38 pathway inhibitor SB202190 AV-951 were stimulated with IL 1B.

Inhibitors,Modulators,Libraries Transwell migration and invasion assays demonstrated that IL 1B stimulation increased the migration and invasion of both AGS and MKN 45 cells. however, IL 1B induced GA cell migration and invasion were significantly attenuated by knockdown of p38 using siRNA or pretreatment with SB202190. Taken together, these data strongly sug gest that IL 1B promoted GA cell migration and invasion are mediated by p38. IL 1B induced activation of p38 upregulates MMP2 and MMP9 e pression and activity in GA cells MMP2 and MMP9 have been shown to play important roles in cancer cell invasion and metastasis.

To e Inhibitors,Modulators,Libraries plore whether MMP2 and MMP9 also participate in the IL 1B induced p38 regulated metastatic potential of GA cells, RT PCR, immunocytochemistry and confocal microscopy, and the zymography assay were carried out to determine MMP2 and MMP9 e pression and activity in GA cell lines transfected with control siRNA or p38 siRNA, or pretreated with or without the p38 inhibitor SB202190, and then treated with or without IL 1B. As e pected, MMP2 and MMP9 e pression and activity were elevated in response to IL 1B treatment.