Anti-cancer effects of COX-2 inhibitors and their correlation with angiogenesis and invasion in gastric cancer.
OBJECTIVE
To observe the anti-cancer effects of COX-2 inhibitors and investigate the relationship between COX-2 inhibitors and angiogenesis, infiltration or metastasis in SGC7901 cancer xenografts.


METHODS
Thirty athymic mice xenograft models with human stomach cancer cell SGC7901 were established and divided randomly into 3 groups of 10 each. Sulindac, one non-specific COX inhibitor belonging to non-steroidal anti-inflammatory drugs (a series of COX inhibitors known as NSAIDs) and celecoxib, one selective COX-2 inhibitor (known as SCIs) were orally administered to mice of treatment groups. Immunohistochemistry was used to examine the expression of PCNA, CD44v6 and microvessel density (MVD). Apoptosis was detected by using TUNEL assay.


RESULTS
Tumors in sulindac and celecoxib groups were significantly smaller than those in control group from the second week after drug administration (P<0.01). In treatment group, the cell proliferation index was lower (P<0.05) and apoptosis index was higher (P<0.05) than those in control groups. Compared with the controls, microvessel density was reduced (P<0.01) and expression of CD44v6 on tumor cells was weakened (P<0.05) in treatment groups.


CONCLUSIONS
COX-2 inhibitors have anticancer effects on gastric cancer. They play important roles in angiogenesis and infiltration or metastasis of stomach carcinoma. The anticancer effects of COX-2 inhibitors may include inducing apoptosis, suppressing proliferation, reducing angiogenesis and weakening invasiveness.
Fu
Suo-Lin
SL
Department of Gastroenterology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China. fusuolin@163.com
Wu
Yun-Lin
YL
Zhang
Yong-Ping
YP
Qiao
Min-Min
MM
Chen
Ying
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology*; D013467:Sulindac / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D013467:Sulindac; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib