Nonsteroidal anti-inflammatory drugs could reverse Helicobacter pylori-induced imbalance between proliferation and apoptosis in gastric epithelial cells

Zhu, GH; Xl, Yang; Lai, KC; Ching, Chi Bun; Wong, Bcy; Wang, Hui; Yuen, ST; Ho, Jcm; Lam, SK

doi:10.1016/s0016-5085(98)81401-7

Cited by 21 publications

(38 citation statements)

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“…However, we found no correlation between cell proliferation and apoptosis in H. pylori-infected and/or NSAID-treated mice, in agreement with the results of other studies (41,66). This observation supports the notion that the induction of apoptosis and proliferation in vivo are independent events regulated by different factors, including the direct effects of H. pylori stimuli and host inflammatory and immune responses, involving cytokines, nitric oxide, gastrin, etc.…”

Section: Discussionsupporting

confidence: 91%

“…Similar findings were reported in a clinical human study (66). From these results, although the mechanism underlying this effect is unclear and complicated, it appears that NSAID administration can suppress uncontrolled apoptosis and proliferation in H. pylori-infected subjects and that this effect might be extended to subsequent processes involving neoplastic changes.…”

Section: Discussionsupporting

confidence: 87%

“…However, in human clinical studies on the interaction of these two factors during cell turnover, some controversial aspects remain unresolved. Zhu et al showed that NSAIDs could abrogate the apoptosis and proliferation enhanced by H. pylori (66). However, Leung et al reported that the eradication of H. pylori prior to NSAID therapy significantly reduced the level of apoptosis in the gastric mucosa (29).…”

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confidence: 99%

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Effects of Nonsteroidal Anti-Inflammatory Drugs on Helicobacter pylori -Infected Gastric Mucosae of Mice: Apoptosis, Cell Proliferation, and Inflammatory Activity

Kim¹,

Lee²,

Lee³

et al. 2001

Infect Immun

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Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are two well-known important causative factors of gastric damage. While H. pylori increases apoptosis and the proliferation of gastric epithelial cells and is an important factor in peptic ulcer and gastric cancer, NSAIDs induce cell apoptosis and have antineoplastic effects. We investigated the effects of NSAIDs (a nonselective cyclooxygenase [COX] inhibitor [indomethacin] and a selective COX-2 inhibitor [NS-398]) on the apoptosis and proliferation of gastric epithelial cells and gastric inflammation in H. pylori-infected mice. C57BL/6 mice were sacrificed 8 weeks after H. pylori SS1 inoculation. Indomethacin (2 mg/kg) or NS-398 (10 mg/kg) was administered subcutaneously once daily for 10 days before sacrifice. The following were assessed: gastric inflammatory activity, gastric COX protein expression by Western blotting; gastric prostaglandin E 2 levels by enzyme immunoassay, apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, and cell proliferation by Ki67 immunostaining. Compared to the controls, H. pylori infection and/or NSAID treatment increased COX-1 and COX-2 protein expression. Gastric prostaglandin E 2 levels, apoptotic index, cell proliferation index, neutrophil activity, and the degree of chronic inflammation were all increased by H. pylori infection, and these effects were significantly decreased by indomethacin treatment. However, NS-398 treatment after H. pylori infection did not induce a significant reduction, although it did result in a tendency to decrease. These results show that NSAIDs can reverse the increased apoptosis and proliferation of epithelial cells and inflammatory activity in the stomachs of H. pylori-infected mice and that, like COX-2 activation, COX-1 induction contributes to the change of gastric mucosal cell turnover and inflammation induced by H. pylori infection.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 87%

mentioning

confidence: 99%

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Effects of Nonsteroidal Anti-Inflammatory Drugs on Helicobacter pylori -Infected Gastric Mucosae of Mice: Apoptosis, Cell Proliferation, and Inflammatory Activity

Kim¹,

Lee²,

Lee³

et al. 2001

Infect Immun

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“…The role of H pylori infection in the gastric carcinogenesis is not clear. It might be involved in imbalance between apoptosis and proliferation [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] . Bcl-2 family members have been closely related to apoptosis, which could either promote cell survival (Bcl-2, Bcl-x L , A1, Mcl-1, and Bcl-w) or promote cell death (Bax, Bak, Bcl-x S , Bad, Bid, Bik, Bim, Hrk, Bok) [34][35][36] .…”

Section: Introductionmentioning

confidence: 99%

Effect ofHelicobacter pyloriinfection on expressions of Bcl-2 family members in gastric adenocarcinoma

Zhang

Fang²,

Wang³

et al. 2004

WJG

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“…Long term co-administration with a COX-2 inhibitor, either celecoxib or nimesulide not only reduced the development of intestinal metaplasia, but also adenocarcinoma [20][21][22] . In human studies, a recent report showed that treatment with NSAIDs for more than 3 mo reversed H pylori-induced harmful effects in gastric epithelial cells [23] . On the other hand, large-scale clinical trials have shown that NSAIDs were effective in the chemoprevention of colorectal neoplasia [5] .…”

Section: Zhang Lj Et Al Celecoxib and Gastric Precancerous Lesionsmentioning

confidence: 99%

Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions

Zhang¹,

Wang²,

Huo³

et al. 2009

WJG

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AIM:To evaluate whether celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, could reduce the severity of gastric precancerous lesions following Helicobacter pylori (H pylori ) eradication.METHODS: H pylori -eradicated patients with gastric precancerous lesions randomly received either celecoxib (n = 30) or placebo (n = 30) for up to 3 mo. COX-2 expression and activity was determined by immunostaining and prostaglandin E 2 (PGE 2 ) assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular density (MVD) assay using CD31 staining. RESULTS:COX-2 protein expression was significantly increased in gastric precancerous lesions (atrophy, intestinal metaplasia and dysplasia, respectively) compared with chronic gastritis, and was concomitant with an increase in cell proliferation and angiogenesis. A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo (P < 0.001). Of these three changes, 84.6% of sites with dysplasia regressed in patients treated with celecoxib (P = 0.002) compared with 60% in the placebo group, suggesting that celecoxib was effective on the regression of dysplasia. COX-2 protein expression (P < 0.001) and COX-2 activity (P < 0.001) in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects. Moreover, it was also shown that celecoxib suppressed cell proliferation (P < 0.01), induced cell apoptosis (P < 0.01) and inhibited angiogenesis with decreased MVD (P < 0.001). However, all of these effects were not seen in placebo-treated subjects. Furthermore, COX-2 inhibition resulted in the up-regulation of PPARg expression, a protective molecule with anti-neoplastic effects.CONCLUSION: H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity, inducing apoptosis, and suppressing cell proliferation and angiogenesis.

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Nonsteroidal anti-inflammatory drugs could reverse Helicobacter pylori-induced imbalance between proliferation and apoptosis in gastric epithelial cells

Cited by 21 publications

References 0 publications

Effects of Nonsteroidal Anti-Inflammatory Drugs on Helicobacter pylori -Infected Gastric Mucosae of Mice: Apoptosis, Cell Proliferation, and Inflammatory Activity

Effects of Nonsteroidal Anti-Inflammatory Drugs on Helicobacter pylori -Infected Gastric Mucosae of Mice: Apoptosis, Cell Proliferation, and Inflammatory Activity

Effect ofHelicobacter pyloriinfection on expressions of Bcl-2 family members in gastric adenocarcinoma

Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions

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