Short-term Celecoxib intervention is a safe and effective chemopreventive for gastric carcinogenesis based on a Mongolian gerbil model

Abstract

AIM:To evaluate the optimal intervention point of a selective cyclooxygenase-2 (COX-2) inhibitor, Celecoxib, for inhibiting Helicobacter pylori (H pylori )-associated gastric carcinogenesis in Mongolian gerbils (MGs). METHODS:One hundred and twelve MGs were divided into six groups (A-F). One hundred gerbils were inoculated with H pylori (groups A-E). Twelve gerbils were inoculated with vehicle broth only (group F). After 4 wk, they were given N'-methyl-N' -nitro-N-nitroso-guanidine (MNNG) (50 mg/mL) in the drinking water for 20 wk. In groups B-E, the animals were given the stock Celecoxib (10 mg/kg per day) diet from the 21st, 31st, 21st and 41st week respectively. The periods of administering Celecoxib were 30, 20, 20, and 15 wk respectively. On the 51st week, the animals were sacrificed for histological examination. Local PCNA expression was examined by the immunohistochemistry method. The expression of COX-2 protein was assessed by Western Blot. Analysis used the χ 2 test. The difference was regarded as significant when P value was less than 0.05. RESULTS:Seventeen percent (17/100) of H pyloriinfected MGs developed gastric cancer. All of these lesions were well-differentiated adenocarcinoma. The incidence rates of adenocarcinoma in groups A-F were 40%, 0%, 0%, 20%, 25%, and 0% respectively. The inflammatory scores were higher in group B than in other groups. There was no inflammatory response noted in group F. Celecoxib treatment resulted in a significant reduction in the proliferation of H pyloriinfected mucosal cells (groups B, C and D) (P < 0.01). The expression of COX-2 protein was significantly attenuated in the groups which were Celecoxib-treated for more than 20 wk (groups B, C, D). The groups treated with Celecoxib had a significantly lower rate of advanced gastric cancer (34% vs 75%, P < 0.001)There were no sudden deaths in any of the groups. CONCLUSION:Short-term treatment with Celecoxib has an anti-carcinogenic effect, and resulted in less severe inflammation and inhibited the invasive degree of gastric cancer.

Synergic effect between 5-fluorouracil and celecoxib on hypoxic gastric cancer cells

“…In addition, chronic NSAID therapy may be able to reduce the risk of colon cancer by 50%, as well as the incidence of esophageal and gastric cancer (26). Studies on animals showed that celecoxib prevented and inhibited gastric cancer carcinogenesis (27,28). The results of the present study demonstrated that celecoxib inhibited the proliferation of SGC7901 gastric cancer cells.…”

Effect of celecoxib plus standard chemotherapy on serum levels of vascular endothelial growth factor and cyclooxygenase-2 in patients with gastric cancer

“…The close association between VEGF and COX-2 and poor prognosis suggest that these two molecules may be used as biomarkers for disease progression, as well as potential therapeutic targets. Multiple in vitro and animal studies indicated that celecoxib may inhibit the growth of gastric tumors and suppress tumor angiogenesis by sensitizing tumor cells to chemotherapy-induced apoptosis (11,12). Celecoxib was demonstrated to be highly potent and relatively non-toxic in animal tumor models.…”

The tumor suppressor microRNA‐29c is downregulated and restored by celecoxib in human gastric cancer cells

“…15,16 Recent studies have also shown that celecoxib has a preventive effect against Helicobacter pylori-associated gastric cancer. 17,18 Therefore, celecoxib has been suggested to have promise for the treatment of gastrointestinal tumors. However, the molecular mechanisms underlying the chemopreventive effects of selective COX-2 inhibitors are not fully understood.…”