| Gastric cancer is one of the most common malignant tumor and a serious threat to human health.It is the fifth most common incident form of cancer worldwide,followed by breast cancer,lung cancer,colorectal cancer and prostate cancer,but the second leading cause of cancer deaths,after lung cancer.In 2013,there were an estimated 984,000 incident cases and 841,000 deaths from gastric cancer in the world.At present,surgery is still considered to be the mainstay for the treatment of gastric cancer.However,the efficacy of the surgical treatment in some patients with advanced or metastatic gastric cancer(A/MGC)remains poor.Thus,seeking another effective way to improve the curative effect of gastric cancer is one of the most important topics in the field of current medical research.As a systemic treatment,chemotherapy plays an important role in the management of patients with gastric cancer,including promoting surgical outcomes,reducing postoperative complications,prolonging the survival period,enhancing survival rate,improving quality of life,relieving symptoms.Some chemotherapy drugs for gastric cancer have been widely used in clinical settings,and have made certain achievements,such as 5-fluorouracil(5-FU),cisplatin,mitomycin,etoposide,paclitaxel,irinotecan,PEGylated adriamycin,but there is still an urgent need to to continue to develop new anti-cancer drugs.Adenosine,a bioactive substance that exists everywhere in human body,was derived from adenosine triphosphate(ATP)release in the presence of the endogenous nucleotide enzyme.Usually,the concentration of adenosine is maintained at a very low level.Adenosine can be transported into cells by transporters or interacts with its receptors on the cell membrane directly,exhibiting a variety of physiological activities,including cell growth,cell differentiation,and cell death.These functions mainly depend on the extracellular concentration of adenosine and the mode of action of adenosine in cells.It has been reported that high concentration of extracellular adenosine can induce apoptosis in multiple types of cancer cells,namely,lung cancer,liver cancer,ovarian cancer and breast cancer.This study aims to determine the effect of adenosine on cell proliferation and apoptosis of human gastric cancer cell line MGC-803 and its mechanism of action,contributing to the development of a new strategy for chemotherapeutic drugs in the treatment of gastric cancer.Objective:To investigate the influence of adenosine on proliferation and apoptosis of human gastric cancer cell line MGC-803 in vitro,and explore its apoptosis mechanism.Methods:The MGC-803 cells were treated with different concentrations of adenosine(0.01-10 mmol/L),and the proliferation of MGC-803 cells was determined using cell counting kit-8(CCK-8)method.The colony formation ability of MGC-803 cells under different concentrations was evaluated by colony formation assay.In addition,Flow cytometry analysis was adopted to analyze the apoptosis of MGC-803 cells upon adenosine treatment.Finally,the expression levels of apoptosis protein Caspase-3 and endoplasmic reticulum stress(ERS)related proteins(casepase-4,p-JNK,CHOP,GRP78)were detected by Western blotting.Results:Adenoaine could significantly inhibit the viability of MGC-803 cells in a concentration-and time-dependent manner(P<0.05).The colony formation of MGC803 cells were dramatically hampered by adenoaine treatment.After treatment with adenosine(0.25,0.5,1 mmol/L)for 24 h,the total apoptosis rate of MGC803 cells was profoundly increased from 4.44±1.4%to 13.2±2.6%,30.6±4.1%,50.9±5.5%(P<0.01).Moreover,the expression of cleaved Caspase-3 was significantly up-regulated on exposure to adenosine(P<0.01).At last,ERS related proteins(casepase-4,p-JNK,CHOP,GRP78)were markedly elevated in adenosine trested group(P<0.05).Conclusion:Adenosine significantly suppressed proliferation and induced apoptosis in MGC-803 cells,while endoplasmic reticulum stress was involved in adenosine-induced apoptosis. |
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