title: Cyclooxygenase-2 inhibition as a strategy for treating gastric adenocarcinoma.
abstract: Cyclooxygenase-2 (COX-2) has been proven to play critical roles in inflammation as well as in cancer. Some studies have shown that the anti-inflammatory, immunosuppressive and anti-arthritic effects of celecoxib are mainly attributed to the inhibition of COX-2 expression. The present study aimed to investigate the function of COX-2 in human gastric adenocarcinoma (GAC). Forty-five cases of human GAC tissues and corresponding adjacent non-cancerous tissues (ANCTs) were collected. The expression of COX-2 and proliferating cell nuclear antigen (PCNA) was assessed using immunohistochemical assay through a tissue microarray procedure. GAC cells (SGC-7901 and MKN-45) in vitro were treated with COX-2 siRNA or different concentrations of celecoxib to observe their effects on cell proliferation, invasion and the underlying molecular mechanisms. As a consequence, the expression of COX-2 and PCNA was found in cancer tissues with a higher strong reactivity rate, compared with the ANCTs (80.0 vs. 53.3%, P=0.011; 68.9 vs. 48.9%, P=0.047), and COX-2 was positively associated with lymph node metastasis of GAC patients (P=0.011). Targeted knockdown of COX-2 inhibited the proliferation, migration and invasion of GAC cells with decreased expression of PCNA. COX-2 inhibitor celecoxib also suppressed the proliferative activities of GAC cells with decreased expression of COX-2 and PCNA. In addition, the tumor volume in the MKN-45 subcutaneous tumor model treated with siCOX-2 was significantly smaller than that of the negative control (NC) group (P<0.01). Taken together, our findings offer a strong preclinical rationale to target COX-2 signaling as a therapeutic strategy to improve the treatment of gastric adenocarcinoma.
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Xiang
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Feng-Qing
authors.initials: FQ
authors.lastname: Hu
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Xiao
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D011720:Pyrazoles; D034741:RNA, Small Interfering; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib