title: Effect of celecoxib on E-cadherin, VEGF, Microvessel density and apoptosis in gastric cancer.
abstract: Cyclooxygenase-2 (COX-2) plays a crucial role in the development and invasion of gastric cancer. COX-2 inhibitors have been shown to be chemopreventive against gastrointestinal cancers. In vitro studies have suggested that the mechanisms may be related to induction of apoptosis and inhibition of angiogenesis. COX-2 may also have impact on E-cadherin. In our study we investigate the effect of Celecoxib on expression of E-cadherin and serum soluble E-cadherin, as well as on apoptosis and angiogenesis in patients with gastric cancer. Fifty nine gastric cancer patients were randomly divided into two groups: Surgery group (n = 22), in which patients underwent surgical resection after diagnosis, and Celecoxib + Surgery group (n = 37), in which patients received oral Celecoxib 200 mg twice daily for 7 days before curative resection. Twenty healthy subjects (Healthy controls) were recruited as normal controls. After curative resection, COX-2, E-cadherin, VEGF, and MVD were detected by immunohistochemistry. Serum soluble E-cadherin was quantitatively measured using a commercially available enzyme-linked immunosorbent assay kit. Apoptosis was determined by TUNEL assay. Significantly decreased expression of COX-2, increased E-cadherin and apoptosis, decreased VEGF and MVD were observed in gastric cancer tissues from patients receiving Celecoxib compared to Surgery group. Compared to Healthy controls, the serum soluble E cadherin levels were higher in gastric cancer patients which were decreased by Celecoxib. This in vivo study demonstrated that Celecoxib induces apoptosis and inhibit angiogenesis of gastric cancer. Its impact on E-cadherin may suggest that this agent may suppress the invasion of advanced gastric cancer.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, the First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Yongning
authors.initials: Y
authors.lastname: Zhou
authors.forename: Juntao
authors.initials: J
authors.lastname: Ran
authors.forename: Chenwei
authors.initials: C
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Honghua
authors.forename: Li
authors.initials: L
authors.lastname: Xingwen
authors.forename: Cheng
authors.initials: C
authors.lastname: Ning
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D015820:Cadherins / Q000096:biosynthesis*; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy; D013449:Sulfonamides / Q000494:pharmacology*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D015820:Cadherins; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D000068579:Celecoxib