Effects of COX-2 inhibitor on growth of human gastric cancer cells and its relation to hepatocyte growth factor.
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.
Chen
Jen-Hao
JH
Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC.
Wu
Chew-Wun
CW
Kao
Hwa-Li
HL
Chang
Hwey-May
HM
Li
Anna F-Y
AF
Liu
Tsung-Yun
TY
Chi
Chin-Wen
CW
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*
D016861:Cyclooxygenase Inhibitors; D017228:Hepatocyte Growth Factor; D051546:Cyclooxygenase 2; D019859:Proto-Oncogene Proteins c-met