title: Effects of COX-2 inhibitor on growth of human gastric cancer cells and its relation to hepatocyte growth factor.
abstract: It is known that hepatocyte growth factor binding to its receptor regulates gastric cancer progression and metastasis. HGF was found to up-regulate the expression of cyclooxygenase-2 gene and increases prostaglandin (PG) synthesis in gastric mucosa cells. Overexpression of COX-2 and increased PG secretion have also been found to be involved in the regulation of growth and metastasis of gastric cancer. Results from this study showed that c-Met and COX-2 are expressed in 28 cases (93.3%) and 16 cases (53.3%) of 30 human gastric cancer tissues, respectively. Expressions of c-Met positively correlated with that of COX-2 (r=0.41; P=0.024). Using in vivo and in vitro models to further examine the interaction between c-MET and COX-2, we found that HGF stimulated the growth of SC-M1 cells in a dose-dependent manner. COX-2-specific inhibitor-NS398 inhibited the growth of human gastric cancer SC-M1 cells as well as HGF stimulated the growth of SC-M1 cells in a dose-dependent manner. HGF treatment of SC-M1 cells increased the secretion of PGE2 and this stimulation was blocked by NS398. In vivo SC-M1 tumor model showed that HGF stimulated the tumor growth and NS398 retarded the tumor growth. These results suggest that COX-2-specific inhibitors may play some role on the therapy of gastric cancer patients with high serum HGF level and overexpression of c-Met in tumor.
authors.affiliation: Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC.
authors.forename: Jen-Hao
authors.initials: JH
authors.lastname: Chen
authors.forename: Chew-Wun
authors.initials: CW
authors.lastname: Wu
authors.forename: Hwa-Li
authors.initials: HL
authors.lastname: Kao
authors.forename: Hwey-May
authors.initials: HM
authors.lastname: Chang
authors.forename: Anna F-Y
authors.initials: AF
authors.lastname: Li
authors.forename: Tsung-Yun
authors.initials: TY
authors.lastname: Liu
authors.forename: Chin-Wen
authors.initials: CW
authors.lastname: Chi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D017228:Hepatocyte Growth Factor; D051546:Cyclooxygenase 2; D019859:Proto-Oncogene Proteins c-met