Effects Of Ursolic Acid And Paclitaxel On COX-2 Expression And Apoptosis In Gastric Cancer Cells

Background:Gastric Cancer is a major public health problem and is the second leading cause of death worldwide in the United States.Every year approximately 670,000 new gastric cancer cases are diagnosed,of which China accounts for 42%.The prognosis of the advanced gastric cancer(AGC)is poor in recent years.The over all 5-year survival rates of AGC are less than 20%in the United States.Chemotherapy is still the most common treatment for patients with gastric cancer.Paclitaxel(PTX)is a kind of alkaloid which is extracted from the bark of Taxus.The PTX disrupts the microtubule function and inhibits the process of cell division,and has shown encouraging activity as a single or combination chemtherapy for the treatment of advanced gastric cancer.Ursolic acid(UA)is widely extracted from many kinds of natural medical herbs.UA is widely used to treat many cancers,which includes melanoma,lung cancer,gastric cancer,colon cancer,etc.Our previous study showed that UA and PTX could significantly inhibit the proliferation of gastric cancer cells via down regulation of COX-2 expression.However,the effect of UA in combination with PTX on apoptosis of gastric cancer cells remains unclear.Objective:To investigate the regulative role of a Chinese medicinal monomer UA,and a chemotherapeutic agent PTX on the COX-2 expression and apoptosis in gastric cancer cell lines,BGC-823 and SGC-7901.Methods:1.BGC-823 and SGC-7901 cells were routinely cultured in RPMI-1640 medium supplemented with 10%heat-inactivated fetal calf serum.Subconfluent cell cultures were treated with UA and/or PTX for 48 h.Acridine Orange/Ethidium Bromide(AO/EB)staining was used to observe the morphologic changes of apoptotic cells.Apoptosis rates were detected by flow cytometric analysis.The expression of COX-2,Bcl-2 and Bax proteins was assessed by western blot analysis.Results:AO/EB staining showed typical apoptotic morphologic changes in BGC-823 cells and SGC-7901 cells.The apoptosis rates were(6.5 ± 1.2)%and(7,0 ± 0.4)%,(9.2 ± 0.5)%and(8.8 ± 1.2)%,(21.3 ± 2.9)%and(20.2 ± 7.3)%in the BGC-823 and SGC-7901 cells treated with UA,PTX,and combination of two agents respectively,which was significantly higher than that in the control group[(3.0 ± 0.5)%and(2.8 ±0.6)%,P<0.01].UA and PTX significantly reduced the expression of COX-2 and Bcl-2 protein and increased Bax protein expression(P<0.05).Conclusion:Both of UA and PTX are able to induce apoptosis in BGC-823 cells and SGC-7901 cells.This apoptosis may be mediated by down-regulation of COX-2 and Bcl-2 and the up-regulation of Bax expression in BGC-823 cells and SGC-7901 cells.The combination of UA plus PTX treatment may have synergistic anticancer role.Background:Helicobacter pylori(H.pylori)gastritis is an infectious disease,eradication of H.pylori is a primary preventive measure for gastric cancer.Epidemiological surveys showed that the infection rate of H.pylori in developing countries was 50%,while the overall rate of adult infection in China was about 56.22%.From 2012 to 2016,Three international consensus on the treatment of H.pylori infection were published,which included H.pylori gastritis's Kyoto global consensus,Consensus on the treatment of adult H.pylori infection in Toronto and Maastricht V/Florence consensus.The consensus points out two aspects of eradication indication and eradication standard.The epidemiological investigation showed a high antibiotic resistance rate to H.pylori eradication therapies.Because of the high incidence of gastric cancer in Jiangsu area,it is very important to investigate the rate of differant medicine resistance to H.pylori and find out the appropriate treatment plan for H.pylori.Objective:To study the prevalence of H.pylori and the antibiotic resistance rate of H.pylori eradication therapy in Jiangsu Province Nanjing District.Methods:The patients,gastric mucosa tissue samples were obtained and cultured from 323 patients with upper abdominal symptoms by gastroenterology.The suspected bacteria tissues were smeared,stained and microscopic scrutinized,and also bio-chemistically tested for H.pylori identification.The H.pylori positive clones were also determined for medicine resistance by K-B tests.190 H.pylori clones were recognized,in which 98 samples were chronic gastrititis,26 samples were gastric ulcers,43 samples were duodenal ulcers and 23 samples were combined ulcers.Results:The results indicated that the positive rate of H.pylori culture in the total samples was 58.8%in those patients,in which the H.pylori positive rate of chronic non-atrophic gastritis was 43.8%(46/105),the H.pylori positive rate of the chronic atrophic gastritis was 56.5%(52/92),the positive rate of H.pylori in the gastric ulcer was 60.5%(26/43),the positive rate of H.pylori in the duodenal ulcer was 76.8%(43/56)and the rate of H.pylori in the combined ulcer was 85.2%(23/27).The resistance rates were also performed on the 190 H.pylori samples.H.pylori has a Metronidazole resistance rate of more than 50%(56.3%),and the drug resistance rate of H.pylori less than 30%were clarithromycin(29.5%),levofloxacin(12.6%),gentamicin(5.3%),amoxicillin(8.9%)and furazolidone(4.2%),respectively.Conclusion:The resistance rates of H.pylori infection to metronidazole and kalamycin were increased in Jiangsu district in recent years.The resistance rates of H.pylori infection to amoxicillin and furazolidone were low in Nanjing area of Jiangsu province.This can provide the evidence for the selection of H.pylori eradication in Jiangsu area.