All e periments using cell lines were cause repeated a minimum 3 times. Data for animal e periments repre sents tumors from three patients. Statistical significance was reported if p value was 0. 05 using an unpaired Student t test. Background Increasing evidence indicates that tumors are promoted and sustained by inflammatory signals from the tumor microenvironment, and the tumor microenvironment plays important roles in the promotion of cancer. Cytokines, especially the cytokines secreted by tumor cells, are essential components of the tumor microenvironment. Tumor necrosis factor alpha, interleukin 1B and IL 6 are the most well characterized cytokines which have been demonstrated to be closely related to cancer progression. A lot of studies have shown that in flammation induced by cytokines plays an important role in the development of gastric cancer.

It is well established that infections, especially those induced by Helicobacter pylori, are capable of inducing gastric mucosal inflammatory responses, resulting in upregulation of IL 1B, which in turn may promote inflammation associated carcinogenesis. However, the underlying molecular mechanisms for the role of IL 1B signaling in gastric carcinogenesis remain largely unknown, and are currently of interest. P38 is a member of the mitogen activated protein kinase superfamily. The MAPK signaling pathways have been well investigated, and are comprised of at least three superfamilies of MAPKs which regulate diverse cellular activities.

It is well known that p38 MAPK is capable of regulating a lot of cellular responses to cytokines and stress, including IL 1B, however, recent data demon strated that p38 is also closely related to the development of different types of human cancer via its ability to elevate cancer cell migration and invasion in response to various stimuli, including inflammatory factors. Additionally, p38 is also involved in the regulation of cell differentiation and apoptosis. Four isoforms of p38 have been identified so far p38, p38 B, p38, and p38. Though the amino acid sequences of these p38 MAPKs are mostly identical, the e pression pattern of each isoform varies. P38 is the major p38 MAPK and is e pressed ubiqui tously, p38 B is mainly e pressed in the brain, whereas p38�� is abundantly e pressed in skeletal muscle and p38 is mainly e pressed in endocrine glands. Many studies have also demonstrated that p38 participates in IL 1B signaling cascades in a set of cell types, especially in mouse embryonic fibroblast cells and macrophages cells, however, very little is known about the function of IL 1B activated p38 in gastric cancer. c Jun N terminal kinase is another MAPK family Drug_discovery member which is also well known to play an important role in regulation IL 1B signaling pathway.