Chemopreventive effects of rofecoxib and folic acid on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

2.50
Hdl Handle:
http://hdl.handle.net/10146/56157
Title:
Chemopreventive effects of rofecoxib and folic acid on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.
Authors:
Fei, Su Juan; Xiao, Shu Dong; Peng, Yan Shen; Chen, Xiao Yu; Shi, Yao
Abstract:
OBJECTIVES: Epidemiological and experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) are chemopreventive agents of gastrointestinal cancers, but few studies on gastric cancer have been carried out. A decrease in folic acid supplement and subsequent DNA hypomethylation are related to gastrointestinal cancers, and it has been shown that high-dose folic acid may interfere with gastric carcinogenesis in dogs. The objective of this study was to investigate the effects of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and folic acid on the chemoprevention of gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats, and to evaluate the cell proliferation of gastric mucosa in different experimental groups. METHODS: Eighty male Wistar rats were randomly divided into five groups (16 rats in each group). In the control group, the rats were given pure water and basal diet. In the MNNG group, the rats received MNNG in drinking water (100 mg/L) and basal diet. In the MNNG + low-dose rofecoxib group, the rats were given MNNG and rofecoxib 5 mg/kg per day with basal diet. In the MNNG + high-dose rofecoxib group, the rats were given MNNG and rofecoxib 15 mg/kg per day with basal diet. In the MNNG + folic acid group, the rats were given MNNG and folic acid 5 mg/kg per day with basal diet. The experiment was terminated at 50 weeks, and all rats were killed. Blood samples of 3 mL were obtained for measurement of serum folic acid concentrations in the control group, the MNNG group and the MNNG + folic acid group by using chemiluminescent method. The stomach was removed from all rats for histopathological examination and immunohistochemical study. Proliferating cell nuclear antigen (PCNA) expression in gastric epithelial cells was also determined. RESULTS: In the MNNG group, five of 11 rats (45.5%) developed gastric cancer, while in all other four groups no gastric cancer was found (P < 0.05). The positivity rate of PCNA expression in the cancerous tissues was significantly higher than that in the non-cancerous tissues (80.0%vs 14.1%, P < 0.05). The positivity rate of PCNA expression in the gastric mucosal cells of the MNNG group was significantly higher than that in the other four groups. The mean serum folic acid concentration of rats was significantly higher in the MNNG + folic acid group (193.70 +/- 60.73 ng/mL) than those in the control group (84.21 +/- 25.26 ng/mL) and the MNNG group (72.27 +/- 16.70 ng/mL, P < 0.05). It was shown that both low- and high-dose rofecoxib as well as folic acid interfered with the development of gastric cancer induced by MNNG in Wistar rats. CONCLUSIONS: The results indicate that rofecoxib as well as folic acid interferes with gastric carcinogenesis induced by MNNG in Wistar rats, and the suppression of gastric cell proliferation may play a crucial role in the chemoprevention of gastric cancer by rofecoxib and folic acid. The higher serum folic acid concentration of rats may play an important role in the prevention of gastric cancer.
Citation:
Chin. J. Dig. Dis. 2006, 7 (3):134-140
Journal:
Chinese Journal of Digestive Diseases
Issue Date:
2006
URI:
http://hdl.handle.net/10146/56157
DOI:
10.1111/j.1443-9573.2006.00258.x
PubMed ID:
16808793
Additional Links:
http://www3.interscience.wiley.com/journal/120718469/abstract
Type:
Article
Language:
en
Description:
Dietary modulation of cancer & cancer biomarkers; Dietary modulation of carcinogenesis-related pathways. Dietary item or component studied: rofecoxib; folic acid. Outcome studied: gastric cancer; proliferating cell nuclear antigen (PCNA)Study type: male Wistar rats Tissue/biological material/sample size: blood; stomach. Impact on outcome (including dose-response): In the MNNG group, five of 11 rats (45.5%) developed gastric cancer, while in all other four groups no gastric cancer was found (P < 0.05). The positivity rate of PCNA expression in the cancerous tissues was significantly higher than that in the non-cancerous tissues (80.0% vs 14.1%, P < 0.05). The positivity rate of PCNA expression in the gastric mucosal cells of the MNNG group was significantly higher than that in the other four groups. The mean serum folic acid concentration of rats was significantly higher in the MNNG + folic acid group (193.70 +/- 60.73 ng/mL) than those in the control group (84.21 +/- 25.26 ng/mL) and the MNNG group (72.27 +/- 16.70 ng/mL, P < 0.05). It was shown that both low- and high-dose rofecoxib as well as folic acid interfered with the development of gastric cancer induced by MNNG in Wistar rats. KEYWORDS - CLASIFFICATION: Adenocarcinoma;Animals;Anticarcinogenic Agents;biosynthesis;blood;Body Weight;Cell Proliferation;chemically induced;China;cytology;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;drug effects;Folic Acid;Gastric Mucosa;humans;Lactones;Male;Methylnitronitrosoguanidine;prevention & control;Proliferating Cell Nuclear Antigen;Rats;Rats,Wistar;Stomach Neoplasms;Sulfones;therapeutic use;
ISSN:
1443-9611
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorFei, Su Juan-
dc.contributor.authorXiao, Shu Dong-
dc.contributor.authorPeng, Yan Shen-
dc.contributor.authorChen, Xiao Yu-
dc.contributor.authorShi, Yao-
dc.date.accessioned2009-03-18T11:03:46Z-
dc.date.available2009-03-18T11:03:46Z-
dc.date.issued2006-
dc.identifier.citationChin. J. Dig. Dis. 2006, 7 (3):134-140en
dc.identifier.issn1443-9611-
dc.identifier.pmid16808793-
dc.identifier.doi10.1111/j.1443-9573.2006.00258.x-
dc.identifier.urihttp://hdl.handle.net/10146/56157-
dc.descriptionDietary modulation of cancer & cancer biomarkers; Dietary modulation of carcinogenesis-related pathways. Dietary item or component studied: rofecoxib; folic acid. Outcome studied: gastric cancer; proliferating cell nuclear antigen (PCNA)Study type: male Wistar rats Tissue/biological material/sample size: blood; stomach. Impact on outcome (including dose-response): In the MNNG group, five of 11 rats (45.5%) developed gastric cancer, while in all other four groups no gastric cancer was found (P < 0.05). The positivity rate of PCNA expression in the cancerous tissues was significantly higher than that in the non-cancerous tissues (80.0% vs 14.1%, P < 0.05). The positivity rate of PCNA expression in the gastric mucosal cells of the MNNG group was significantly higher than that in the other four groups. The mean serum folic acid concentration of rats was significantly higher in the MNNG + folic acid group (193.70 +/- 60.73 ng/mL) than those in the control group (84.21 +/- 25.26 ng/mL) and the MNNG group (72.27 +/- 16.70 ng/mL, P < 0.05). It was shown that both low- and high-dose rofecoxib as well as folic acid interfered with the development of gastric cancer induced by MNNG in Wistar rats. KEYWORDS - CLASIFFICATION: Adenocarcinoma;Animals;Anticarcinogenic Agents;biosynthesis;blood;Body Weight;Cell Proliferation;chemically induced;China;cytology;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;drug effects;Folic Acid;Gastric Mucosa;humans;Lactones;Male;Methylnitronitrosoguanidine;prevention & control;Proliferating Cell Nuclear Antigen;Rats;Rats,Wistar;Stomach Neoplasms;Sulfones;therapeutic use;en
dc.description.abstractOBJECTIVES: Epidemiological and experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) are chemopreventive agents of gastrointestinal cancers, but few studies on gastric cancer have been carried out. A decrease in folic acid supplement and subsequent DNA hypomethylation are related to gastrointestinal cancers, and it has been shown that high-dose folic acid may interfere with gastric carcinogenesis in dogs. The objective of this study was to investigate the effects of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and folic acid on the chemoprevention of gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats, and to evaluate the cell proliferation of gastric mucosa in different experimental groups. METHODS: Eighty male Wistar rats were randomly divided into five groups (16 rats in each group). In the control group, the rats were given pure water and basal diet. In the MNNG group, the rats received MNNG in drinking water (100 mg/L) and basal diet. In the MNNG + low-dose rofecoxib group, the rats were given MNNG and rofecoxib 5 mg/kg per day with basal diet. In the MNNG + high-dose rofecoxib group, the rats were given MNNG and rofecoxib 15 mg/kg per day with basal diet. In the MNNG + folic acid group, the rats were given MNNG and folic acid 5 mg/kg per day with basal diet. The experiment was terminated at 50 weeks, and all rats were killed. Blood samples of 3 mL were obtained for measurement of serum folic acid concentrations in the control group, the MNNG group and the MNNG + folic acid group by using chemiluminescent method. The stomach was removed from all rats for histopathological examination and immunohistochemical study. Proliferating cell nuclear antigen (PCNA) expression in gastric epithelial cells was also determined. RESULTS: In the MNNG group, five of 11 rats (45.5%) developed gastric cancer, while in all other four groups no gastric cancer was found (P < 0.05). The positivity rate of PCNA expression in the cancerous tissues was significantly higher than that in the non-cancerous tissues (80.0%vs 14.1%, P < 0.05). The positivity rate of PCNA expression in the gastric mucosal cells of the MNNG group was significantly higher than that in the other four groups. The mean serum folic acid concentration of rats was significantly higher in the MNNG + folic acid group (193.70 +/- 60.73 ng/mL) than those in the control group (84.21 +/- 25.26 ng/mL) and the MNNG group (72.27 +/- 16.70 ng/mL, P < 0.05). It was shown that both low- and high-dose rofecoxib as well as folic acid interfered with the development of gastric cancer induced by MNNG in Wistar rats. CONCLUSIONS: The results indicate that rofecoxib as well as folic acid interferes with gastric carcinogenesis induced by MNNG in Wistar rats, and the suppression of gastric cell proliferation may play a crucial role in the chemoprevention of gastric cancer by rofecoxib and folic acid. The higher serum folic acid concentration of rats may play an important role in the prevention of gastric cancer.en
dc.language.isoenen
dc.relation.urlhttp://www3.interscience.wiley.com/journal/120718469/abstracten
dc.subjectchemopreventionen
dc.subjectcyclooxygenase-2 inhibitoen
dc.subjectfolic aciden
dc.subjectproliferating cell nuclear antigenen
dc.subjectrofecoxiben
dc.subjectstomach neoplasmen
dc.subject.meshAdenocarcinoma-
dc.subject.meshAnimals-
dc.subject.meshAnticarcinogenic Agents-
dc.subject.meshBody Weight-
dc.subject.meshCell Proliferation-
dc.subject.meshFolic Acid-
dc.subject.meshGastric Mucosa-
dc.subject.meshLactones-
dc.subject.meshMale-
dc.subject.meshMethylnitronitrosoguanidine-
dc.subject.meshProliferating Cell Nuclear Antigen-
dc.subject.meshRats-
dc.subject.meshRats, Wistar-
dc.subject.meshStomach Neoplasms-
dc.subject.meshSulfones-
dc.titleChemopreventive effects of rofecoxib and folic acid on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.en
dc.typeArticleen
dc.identifier.journalChinese Journal of Digestive Diseasesen
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