There fore, upregulation of MMP2 and MMP9 are crucial for IL 1B induced GA cell migration and invasion. IL 1B induced activation of JNK doesnt participate in regulation of GA cell migration and invasion It is well known that members of MAPK play important roles in regulation of cellular responses to cytokines and stress, and P38 and JNK are the major MAPK family members that regulate IL 1B signaling pathways. To understand whether JNK is also associated with IL 1B induced GA cell migration and invasion, Western blot analysis was performed to detect the activation of JNK in response to IL 1B. As e hibited in Figure 5A, p JNK was detected in both AGS and MNK 45 cell lines after stimulation with IL 1B for 30 min.

However, the results of both Transwell migration and invasion assays showed that the increased migration and invasion of both AGS and MKN 45 cells induced by IL 1B stimulation were not attenuated by knockdown JNK with siRNA nor attenuated by inhibition JNK pathway with JNK inhibitor SP600125 neither, The number of migrated and invasive cells almost did not showed change before or after transfection with siRNA against JNK or with or without pre treated with JNK inhibitor SP600125. JNK was not associated with IL 1B promoted the GA cell migration and invasion having been further verified by AP 1 luciferase reporter assay. As the upstream kinase of c jun, JNK is able to activate AP 1, and the activation of AP 1 by JNK is closely related with JNKs function on regulation of various cellular reaction including cancer cell migration and invasion, however, IL 1B induced AP 1 activation in both AGS and MKN 45 cells was not inhibited by JNK siRNA nor JNK inhibitor SP600125 neither.

All together, these data strongly indicate that the increased GA migration and invasion promoted by IL 1B are not regulated by JNK. Phospho AV-951 p38 is upregulated and correlates with the e pression of IL 1B, MMP2, MMP9 and c fos in human GA tissues The e pression of p p38 in a series of 105 GA tissues and the paired non neoplastic gastric tissues was e amined by immunohistochemistry. Of the 105 cancer samples, 53 cases of GA tissues e hibited over e pression of p p38 compared to the paired non neoplastic gastric tissues. Positive p p38 e pression was frequently observed in both the GA cell cytoplasm and nucleus. No significant associations were observed between overe pression of p p38 in the patients age, gender, tumor size, histological type, or grade of differentiation. However, overe pression of p p38 displayed significantly related with lymph node metastasis, and invasion beyond the serosa. These data suggest that overe pression of p p38 is associated with metastasis in human GA.