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The Inhibition Effects Of 18?-glycyrrhetinic Acid On Carcinogenesis And Expressions Of MiRNAs In Gastric Cancer

Posted on:2018-11-06Degree:MasterType:Thesis
Country:ChinaCandidate:Y E SuoFull Text:PDF
GTID:2334330515983106Subject:Clinical Medicine
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Background: Gastric cancer is a common malignant tumor with high morbidity and mortality.At present,the research on chemoprevention of gastric cancer is mainly focused on the eradication of Helicobacter pylori,antioxidants,folic acid and selective cyclooxygenase inhibitors.Due to the enhancement of the drug resistance of Helicobacter pylori,the efficiency of the drug was gradually affected.Therefore,the exploration of new drugs,drug targets and the mechanism of drug resistance is of great importance.Glycyrrhetinic acid is one of the main active ingredients of licorice.It has many physiological activities,including anti-inflammatory,anti ulcer,anti-virus,anti-tumor,anti liver toxin and immunoregulatory function.Glycyrrhetinic acid has been shown to inhibit gastric cancer in vitro and in vivo,so it may be a new chemopreventive agent for gastric cancer.The gastric cancer mouse model K19-C2 m E was able to develop a spontaneous tumor in the proximal stomach,and the growth of the tumor was similar to that of human,it was an ideal gastric cancer model for research.Micro RNA is a class of small non coding single stranded RNA.This kind of RNA can regulate the expression of oncogenes or tumor suppressor genes,and the research of these RNA will be a new treatment for cancer.Objective:To investigate the effect of glycyrrhetinic acid on the development of gastric cancer in transgenic mice by affecting the expression of mi RNA.To investigate whether mi RNA can inhibit the proliferation of human gastric cancer cells,and tostudy its effects on proliferation,apoptosis and cell cycle of human gastric cancer cells.Methods:We established K19-C2 m E transgenic mouse model of gastric cancer.The 6 week old mice were divided into the control group(n = 40)and the glycyrrhetinic acid-treated group(n = 40),and the rats were sacrificed and dissected at the age of 52 weeks.The mi RNA expression of two groups of mice gastric cancer tissues were analyzed.The expression of mi RNA of glycyrrhetinic acid-treated gastric cancer cell lines MKN-1 and BGC-823 was also analysed.Furthermore,we investigated the effect of mi RNA expression on gastric cancer cells.The changes of mi RNA expression in mice gastric cancer tissue and gastric cancer cells were analyzed by statistical analysis software.Results:Glycyrrhetinic acid could significantly reduce the incidence of gastric cancer in transgenic mice(P=0.002),the tumor incidence rate in the control group is 77.8%(28/36),the gastric cancer incidence rate in glycyrrhetinic acid group is 33.3%(13/39);Glycyrrhetinic acid can change the expressions of mi RNAs in gastric cancer tissue,38 kinds of mi RNAs in mouse tumors(fd?2 or fd?0.5,P<0.01)was changed;Among the difference of mi RNAs in mice gastric carcinoma treated by glycyrrhetinic acid mi R-149-3p was the highest,compared with the control group;Glycyrrhetinic acid treatment of gastric cancer cell lines BGC-823 and MKN-1 after the expression of mi R-149-3p in a time and dose-dependent manner;Mi R-149-3p can inhibit MKN-1 and BGC-823 human gastric cancer cell proliferation,promote cell apoptosis.
Keywords/Search Tags:18?-Glycyrrhetinic acid, Gastric cancer, Micro RNA, Chemoprevention, Transgenic mice
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