Helicobacter pylori infection, gastrin, cyclooxygenase-2, and apoptosis in colorectal cancer

Abstract

Helicobacter pylori (HP) infection is usually accompanied by an increased plasma level of gastrin, a potent mitogen able to induce cyclooxygenase (COX)-2. This study examined (a) the seroprevalence of HP, its cytotoxic protein, CagA, and cytokines (tumor necrosis factor alpha, interleukins 1beta and 8) in 80 patients with colorectal cancers, before and after the removal of tumor, compared with 160 age- and gender-matched controls; (b) the gene expression of gastrin and its receptors (CCKB-R) in the cancer tissue, (c) the plasma levels and tumor tissue contents of gastrin, and (d) the mRNA expression of COX-1, COX-2, and apoptotic proteins (Bax and Bcl2) in cancer tissue and intact colonic mucosa. Anti-HP IgG, anti-CagA IgG seroprevalence, and cytokine levels were analyzed by enzyme-linked immunosorbent assay tests; gene expressions of gastrin, CCKB-R, COX-1, COX-2, Bax, and Bcl2 by reverse transcriptase polymerase chain reaction; and gastrin by radioimmunoassay. The seroprevalence of HP, especially that expressing CagA, was significantly higher in cancer patients than in controls and did not change 1 week after tumor resection while plasma cytokines were significantly reduced after this operation. Both gastrin and CCKB-R mRNA were detected in the cancer tissue and the resection margin; similarly, COX-2 mRNA was expressed in most of cancers and their resection margin but not in intact colonic mucosa, where only COX-1 was detected. The colorectal cancer tissue contained several folds more immunoreactive gastrin than cancer resection margin and many folds more than the intact colonic mucosa. We conclude that colon adenocarcinoma and its resection margin overexpress gastrin, its receptors, CCKB-R, and COX-2, and that HP infection may contribute to colonic cancerogenesis via overexpression of gastrin and COX-2, which may account for the stimulation of the tumor growth and the reduction in apoptosis as documented by enhanced mRNA expression of anti-apoptotic Bcl2 over proapoptotic Bax proteins.

Seroprevalence of Helicobacter pylori in patients with colon adenomas in a brazilian university hospital

“…These findings are in accordance with those of some other studies in which a similar methodology was used. Some of these studies found a greater prevalence of the bacteria in patients with colon adenomas or adenocarcinomas than in those of the control group (1,2,5,6,10,11,23,24,30) . However, different results from those of our study and of the above studies were also reported.…”

“…The observation that chronic H. pylori infection promotes hypergastrinemia and that colon neoplasias also develop with an increase of gastrin serum led several authors to evaluate the possible association between the bacteria and the adenomas and adenocarcinomas of the colon. Epidemiological studies showed a greater prevalence of adenomas and/or adenocarcinomas in patients infected with H. pylori (2,5,10,11,23,24,30) . This association is, however, controversial because other researchers did not identify any association between adenomas and/or colon adenocarcinomas and infection caused by H. pylori (18,25,31,35) .…”

Association between Helicobacter pylori seropositivity anddigestive tract cancers

“…Hartwich et al [35] found a positive association between colon adenocarcinoma risk and H pylori seropositivity, especially CagA + strains. However, there are also reports indicating no association between H pylori seroprevalence and colorectal neoplasia [36,37] .…”

Growth inhibitory activity of ethanol extracts of Chinese and Brazilian propolis in four human colon carcinoma cell lines

“…p53-independent pathways may be involved but this issue warrants further investigation. Most patients with colorectal carcinoma present an increased expression of cyclooxygenase-2 (COX-2) in their neoplastic tissues (30). Thus, we also examined the expression levels of COX-2 mRNA in HT29 cells since these cells highly express COX-2 that is only slightly expressed by HCT116 cells (31,32).…”