Relationship Between ADH Expression With Characteristics Of Gastric Cancer And The Biological Effect Of Alcohol On Gastric Cancer Cells

Background and aim:Gastric cancer is one of the most common malignant tumor in the world and has high mortality and morbidity. It is caused by the result of long-term and multiple factors, and the incidence of gastric cancer are significant different in varied nation and region.The exact cause of gastric cancer has not yet been fully elucidated. Studies have shown that Helicobacter pylori infection, diet, smoking and genetic susceptibility of the host are important factors of gastric cancer. Risk related to drinking and gastric cancer is still controversial. Intaking alcohol can stimulate the gastric mucosa directly, and acetaldehyde, the metabolic intermediate item of alcohol, can cause gastric mucosal injury. Gastric epithelial susceptible affected by carcinogenic substance directly,and it can cause malignant transformation. Alcohol dehydrogenase (ADH) plays a vital role in alcohol metabolism process, which is mainly distributed in the liver, the distribution of a small amount in the gastrointestinal tract and other organs. ADH, the rate-limited enzyme of alcohol metabolism, can influence on local tissue blood alcohol concentration. It is one of the decisive factors affecting the body’s Drinking process. Relationship between ADH levels and gastric cancer are still not clear. We studied on collected tissue specimens and clinical data of patients with gastric cancer. The aim of the study was to analyze the relationship between the clinical pathological characteristics, alcohol consumption and ADH expression. And the study also investigated the influence of diverse concentrations of alcohol on gastric adenocarcinoma cell viability, apoptosis, and the expression changes of ADH with alcohol management.Methods:1. The expression of ADH in a tissue microarray containing101gastric cancer and67paracancer in those spots of gastric cancer tissues was detected by immunohistochemical technique. The correlation among the expression of the ADH and clinicopathalogic variables and overall survival of the gastric cancer was analyzed.2. Gastric adenocarcinoma cell lines (MGC803, BGC823and SGC7901) were treated with different concentrations of alcohol (0.03125%,0.0625%,0.125%,0.25%,0.5%,1%,2%,4%and6%). An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry were used to analyze the effect of alcohol treatment on cell viability and apoptosis.3、Western blotting was used to analyze the expression of ADH in gastric carcinoma cells treated with different concentrations of alcohol (0.125%,0.25%,0.5%). Results:1,39.6%of101gastric cancer were positive for ADH expression, and47.76%of67gastric paracancer were positive for ADH expression. The expression of ADH in paracancer tissue was correlated with the prognosis in gastric cancer. One-way Anova analyses showed that gastric ADH expression differed in patients with different volumn of alcohol consumption. Alcohol consumption, TNM stage was closely correlated to overall survival(P<0.05).2, Alcohol treatment inhibited cell proliferation in gastric adenocarcinoma cell lines in a significant dose-dependent manner. Alcohol was also able to induce the apoptosis of gastric adenocarcinoma cells in a dose-dependent manner.3, ADH activity of gastric adenocarcinoma cells increased with the increase of the concentration of alcohol.Conclusions:1. The age,tumor TNM stage would be the predictive factors of gastric cancer prognosis, and gastric ADH expression level may be relevant to gastric cancer prognosis.2、Alcohol inhibited cell viability and growth of gastric adenocarcinoma cell lines. Low concentrations of alcohol also induced apoptosis of the gastric adenocarcinoma cell lines.3、Alcohol increased the expression of ADH of the gastric adenocarcinoma cell lines.