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Omeprazole Promotes Carcinogenesis of Fore-Stomach in Mice With Co-Stimulation of Nitrosamine

Omeprazole Promotes Carcinogenesis of Fore-Stomach in Mice With Co-Stimulation of Nitrosamine

Lei Huang, Dong-Jiang Qi, Wei He, A-Man Xu

Oncotarget. 2017 Jul 31;8(41):70332-70344.

PMID: 29050283

Abstract:

Objectives:
To investigate if oral omeprazole application induces cancers of fore and glandular stomach in mice.
Methods:
A total of 66 eligible male mice were randomly divided into 6 groups, which were treated with control reagent, low (6 mg/kg) and high dose omeprazole (30 mg/kg), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 100 mg/L water), and MNNG plus low and high dose omeprazole, respectively. After 24 weeks, concentrations of acid phosphatase (ACP) and N-acetyl-β-D-glucosaminidase(NAG) in serum and spleen was examined, and p21 and mTOR levels in stomach were detected.
Results:
The mouse spleen weight index was smaller in the omeprazole group than the control group, and in the MNNG plus omeprazole groups than the MNNG group. In the fore-stomach, more carcinomas were observed in the MNNG plus omeprazole groups than in the MNNG group. In the glandular stomach, there existed more atypical hyperplasia cases in the MNNG plus omeprazole groups than the MNNG-treated group, and one carcinoma was induced in the MNNG plus high dose omeprazole group. Omeprazole alone caused minor gastric pathological changes. Omeprazole treatment lowered both serum and spleen ACP and NAG levels in both the non-MNNG-treated and MNNG-treated subgroups. In fore-stomach, there existed decreased p21 and mTOR levels in the omeprazole-treated groups than in the control group, and in the MNNG plus omeprazole groups than the MNNG-treated group.
Conclusion:
Omeprazole promotes carcinogenesis of the mouse fore-stomach but not the glandular stomach following treatment with MNNG. Lysosomal hydrolase activity was inhibited and some cancer-associated proteins was dysregulated, which requires further explorations.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
CS3103117	N′-Methyl Omeprazole			Price

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