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ABSTRACT: A recent study reported that in addition to their inhibitory effect on gastric acid secretion, some proton pump inhibitors also exert a cytoprotective effect on the gastric mucosa. We investigated the effects of lansoprazole (LPZ) on the epithelial cell cycle, and on the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2).
We examined the effects of 25 and 5 mg/kg LPZ on ulcer healing in an acetic acid-induced ulcer model in rats with and without indomethacin (IND) treatment. On days 14 and 28 after ulcer formation, we compared the ulcer diameter, bromodeoxyuridine (BrdU) uptake, apoptosis, vascular density, and the expressions of VEGF and MMP-2 in the different groups.
LPZ administration increased the BrdU uptake that was reduced by IND administration. LPZ administration also increased VEGF expression at the ulcer margin in a dose-dependent manner. However, LPZ administration did not increase VEGF expression following IND pretreatment. Administration of IND alone significantly decreased MMP-2 expression at the ulcer margin; on the other hand, subsequent administration of LPZ increased the MMP-2 expression.
One of the mechanisms of ulcer healing brought about by LPZ may be the involvement of endogenous prostaglandin (PG) secretion. The effect of endogenous PG secretion may be related to the induction of VEGF expression. On the other hand, LPZ administration increased MMP-2 expression, and this effect was not influenced by the inhibition of PG synthesis. The mechanisms of LPZ on ulcer healing may be involved by VEGF expression through endogenous PGs secretion. Additionally, the stimulated expression of MMP-2, which is not secreted by endogenous PGs, is another important factor for ulcer healing by LPZ.
Journal of Gastroenterology 03/2010; 45(8):846-58. · 4.16 Impact Factor
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ABSTRACT: The overexpression of murine double minute 2 (MDM2) is found in several human tumors, and increased expression of MDM2 inactivates the apoptotic and cell cycle arrest function of p53. Interleukin-16 (IL-16) is a pleiotrophic cytokine and the properties of IL-16 suggest that it involve in the pathophysiological process of chronic inflammatory diseases. In this study, we investigated the expression of MDM2 in intestinal metaplasia and gastric cancer as well as the effect of H. pylori infection and IL-16 on epithelial cell proliferation and MDM2 expression in gastric cells in vitro. The expression of MDM2 on gastric biopsies was studied immunohistochemistry. AGS cells were incubated with a combination of IL-16 and Helicobacter pylori (H. pylori). Gastric epithelial cell proliferation was studied by BrdU uptake and the expressions of MDM2 were studied by ELISA. There was no significant difference on the expression of MDM2 between with and without H. pylori infected chronic gastritis. In H. pylori infected gastric mucosa; the MDM2 expression was higher on intestinal metaplasia and gastric cancer than chronic gastritis. IL-16 administration was increased MDM2 expression and cell proliferation on AGS cells, which was decreased by H. pylori infection. In conclusion, the expression of MDM2 in long-term H. pylori infected gastric mucosa may indicate a risk for carcinogenesis. IL-16 secretion in H. pylori infected mucosa is one of the factors for gastric cancer. The expression of MDM2 on mucosa can be a mediator for gastric cancer.
Journal of Clinical Biochemistry and Nutrition 04/2009; 44(2):196-202. · 1.98 Impact Factor
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ABSTRACT: Recently the finding of gastric cancer in Helicobacter pylori (H. pylori)-infected mouse models was reported. Studies of humans and animal models have shown that H. pylori infection stimulates gastric epithelial cell proliferation and apoptosis. Polyphenols contained in green tea and related compounds were reported to have a variety anti-tumor effects and bactericidal properties. We studied the effect of green tea polyphenols on gastric cell proliferation and apoptosis in an H. pylori-infected mouse model. This model was prepared by inoculating Balb/c mice with 10(8) cfu of H. pylori (NCTC 11637 strain) by gavage. Beginning 18 weeks after inoculation, 0.5% polyphenols were given in drinking water every day for 2 weeks. Mice were sacrificed 1 h after bromodeoxyuridine (BrdU) was given i.p. for preparation of paraffin-embedded specimens. Cell proliferation and apoptosis were examined by the avidin-biotin complex method using anti-BrdU antibody and the TUNEL method, respectively. H. pylori infection resulted in increased BrdU-labeled cells in both the antrum and the bodies. Administration of polyphenols suppressed this increased proliferation. H. pylori infection increased apoptotic cells in both the antrum and the corpus in comparison with controls. This increase was not seen in H. pylori-infected mice given polyphenols. We conclude the administration with polyphenols might suppress gastric carcinogenesis that is in part related to H. pylori infection.
Journal of Clinical Biochemistry and Nutrition 04/2007; 40(2):108-15. · 1.98 Impact Factor
