BACKGROUNDInfection with Helicobacter pylori (H. pylori) may lead to chronic inflammation of the stomach epithelium, mucosal atrophy, imbalance of proliferation and apoptosis of epithelial cells; resulting in chronic gastritis, peptic ulcer, gastric cancer, and many other clinical outcomes. Why and how H. pylorus leads to gastric cancer is not clear yet. Through in vitro experiments, this study evaluated the effects of broth culture filtrate protein (BCF-P) from the supernatant of liquid culture media of H. pylori on proliferation and apoptosis of immortalized human gastric epithelial cell lines (GES-1) and gastric cancer cell lines (AGS).

METHODSFor the study, GES-1 and AGS cell lines mix with BCF-P and epidermal growth factor (EGF). MTT assay and flow cytometry (FCM) determined the levels of proliferation and apoptosis. Detected expression levels of cyclooxygenase-2 (COX-2) and Fas mRNA by reverse transcription (RT)-PCR. Also did analysis of the effects of BCF-P on epidermal growth factor receptor (EGFR) tyrosine kinase activity of GES-1 and AGS cells by non-radioactive enzyme-linked assay. The Student's t test and one-way analysis of variance (ANOVA) were used for statistical analysis.

RESULTSBCF-P inhibited proliferation of GES-1 and AGS cells in a concentration-dependent manner. The inhibition rates are respectively 68.7% in AGS and 61.4% in GES-1. With the same dose and time for inhibiting the proliferation, BCF-P failed to induce apoptosis of GES-1 and AGS cells. Effects of BCF-P reduced the expression of Fas mRNA of GES-1 and AGS cells (P < 0.05). This is consistent with the effects of EGF. BCF-P reduced the expression of COX-2 mRNA of AGS cells (P < 0.05). This is opposite to the effects of EGF (P < 0.05). Effects of BCF-P improved more than three times the EGFR tyrosine kinase activity of GES-1 and AGS cells.

CONCLUSIONSBCF-P inhibited the proliferation of AGS and GES-1 cells in vitro, unrelated to apoptosis. Effects of BCF-P on gastric epithelial cells in vitro are not equivalent to that of EGF.

Apoptosis ; drug effects ; Bacterial Proteins ; toxicity ; Cell Proliferation ; drug effects ; Culture Media ; Cyclooxygenase 2 ; genetics ; Epidermal Growth Factor ; pharmacology ; Gastric Mucosa ; drug effects ; pathology ; HeLa Cells ; Helicobacter pylori ; pathogenicity ; Humans ; RNA, Messenger ; analysis ; fas Receptor ; genetics

Most gastric cancers are caused by infection with the common human bacterial pathogen, Helicobacter pylori. It is now accepted that gastric cancer can be prevented and virtually eliminated by H. pylori eradication and this knowledge was responsible for country-wide H. pylori eradication combined with secondary cancer prevention for those with residual risk that was introduced in Japan in 2013. Korea is a high H. pylori prevalence and high gastric cancer incidence country and a good candidate for a gastric cancer elimination program. The presence of an H. pylori infection is now considered as an indication for treatment of the infection. However, antimicrobial drug resistance is common among H. pylori in Korea making effective therapy problematic. Country-wide studies of the local and regional antimicrobial resistance patterns are needed to choose the most appropriate therapies. H. pylori and gastric cancer eradication can be both efficient and cost effective making it possible and practical to make Korea H. pylori and gastric cancer free. There is no reason to delay.
Anti-Bacterial Agents/*therapeutic use ; Disease Eradication ; Drug Resistance, Bacterial ; Helicobacter Infections/*drug therapy/epidemiology/microbiology ; Helicobacter pylori/*drug effects/growth & development ; Humans ; Prevalence ; Primary Prevention/*methods ; Republic of Korea/epidemiology ; Risk Assessment ; Risk Factors ; Stomach Neoplasms/epidemiology/microbiology/*prevention & control ; Treatment Outcome