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Objective An investigation was conducted to assess the effects and mechanism of celecoxib [a selective cyclooxygenase(COX) 2 inhibitor] on a rat colitis model induced by trinitrobenzene sulfonic acid (TNBS). Methods The rats were divided into four groups. Group 1 and group 2 were experimental groups. Group 3 and group 4 were control groups. Colitis was induced by intracolonic administration of TNBS (25 mg/ml) in a vehicle of 50% ethanol (0.25 ml) in rats of experiment groups. Three hours before induction of colitis ,the rats were beginning and continuing to treat orally with celecoxib (1.25 mg/kg, group 1) and distilled water (1 ml/0.3 kg, group 2) twice per day for 7 days , respectively. The rats in group 4 were treated orally with celecoxib (1.25 mg/kg) twice per day for 7 days. Group 3 served as healthy control. All rats that survived until the end of the experiment (7 d) were killed and the severity of damage were assessed. The prostaglandin E2 (PGE2) concentrations of colonic mucosa were tested by radioimmunoassay. Results The colonic damage scores were 11.15?3.3 in group 1 and 8.50?2.82 in group 2. Both were significantly higher than that of group 3 (0.62?0.09)( P
ABSTRACT
Objective An investigation was conducted to assess the chemopreventive effects of celecoxib, a selective cyclooxygenase(COX)-2 inhibitor, on a rat colon carcinogenesis model induced by dimethylhydrazine (DMH). The results were compared with those of sulindac. Methods Thirty-two 8-week-old female Sprague-Dawley rats were randomly divided into four groups (n=8 each):Group A rats were treated with DMH(120 mg/kg wt, single subcutaneous injection) alone and group B rats were treated with saline alone. Group C rats were pre-treated with sulindac (320 mg/kg feedstuff) and group D rats pre-treated with celecoxib (1500 mg/kg feedstuff) for 7 days before DMH initiation. The animals were killed at the end of the experiment (week 5) and the aberrant crypt foci(ACF) and aberrant crypt(AC) of the colonic mucosa were assessed after being stained with methylene blue. Results In group A(DMH only), the average numbers of ACF and AC were 182.4?93.43 and 262.8?197.8 respectively. In group B (saline group) rats, no ACF was found. In group C (sulindac group) rats, the average numbers of ACF and AC were 91.25?48.98 and 139.60?68.52 respectively, both of them were decreased significantly as compared with those in Group A (P
ABSTRACT
Objective To compare the effect of seven commonly used nonsteroidal anti inflammatory drugs (NSAIDs) on proliferation, apoptosis, and neoplasmagenesis of gastric cancer cells in vivo. Methods Gastric cancer cell lines were treated with NSAIDs (aspirin 0-400 ?mol/L, indomethacin 0-25 ?mol/L, and ibuprofen, naproxen, sulindac, nimesulide, celecoxib 0-200 ?mol/L, respectively). Proliferation of the cells was detected by using MTT assay. Apoptosis of cells was measured by using fluorescence activated cell sorter (FACS). Nude mice bearing gastric cancer xenografts were administrated with NSAIDs (indomethacin 3 mg/kg, sulindac 8 mg/kg, nimesulide 6 mg/kg, celecoxib 15 mg/kg) for 30 days, and then the weight of implanted tumors was measured. Results There was a dose dependent inhibition of cell proliferation by majority of NSAIDs used, celecoxib the most, except for ibuprofen and naproxen. In nude mice, NSAIDs also showed a suppressive effect on tumor growth with inhibitory rate of celecoxib as (93.8?0.97)%, nimesulide (93.1?1.78)%, indomethacin (89.9?5.61)% and sulindac (89.3 ? 2.07)%. Once incubated with celecoxib and indomethacin, the gastric cancer cells went to apoptosis with an increase in percentage of apoptotic cells up to 30.4% and 23.9%, respectively. Conclusions Many NSAIDs, celecoxib in particular, appeared to be suppressive to gastric cancer cells with exception for ibuprofen and naproxen. Induction of apoptosis might be one of the mechanisms that NSAIDs inhibit gastric cancer.
ABSTRACT
Objective To study the effect of a selective COX-2 inhibitor Celecoxib on cell proliferation and apoptosis of human coloretal cancer cell line HT-29 to seek an effective and safe drug for colon cancer chemoprevention. Methods Using MTT assay, flow cytometry(FCM), acridine orange and ethidium bromide staining, the effect of celecoxib on the proliferation and apoptosis of HT-29 cells were investigated. Results The growth of HT-29 cells was inhibited by celecoxib in a dose- and time- dependent manners. FCM analysis showed that the treated HT-29 cells had typical Sub-G 1 peak, the apoptotic rate of which was (7 31?2 37)%～(48 3?2 86)%. The cell ratio of G 0/G 1 phase increased, whereas the cell ratio of S and G 2/M phases decreased after treatment, which was in a dose-dependent manner as well. The treated HT-29 cells exhibited some morphological features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation, and the formation of apoptosis bodies, the apoptotic index of which was in a dose- and time- dependent manners. Conclusions Celecoxib inhibited proliferation and induced apoptosis of human colorectal cancer cell line HT-29, which may be related to blocking the cell cycle progress of HT-29 cells.