Effect Of AHVAC-Ⅰ On Exosome Secretion To Inhibit Gastric Cancer Cell Metastasis

Objective:Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related death in the world.In our country,the incidence and mortality of gastric cancer（GC）are very high.Although the combination of surgery,chemotherapy,radiotherapy and immunotherapy has improved survival in these patients,most of them still experience relapse and metastasis,which leads to a poor prognosis.Recent studies have revealed that Exosome-derived from GC cells play crucial roles in the tumorigenesis,progression and drug resistance of GC.In the present study,we investigate the relationship between serum Exosome particle size and the prognosis of gastric cancer.And then we study the effect of AHVAC-Ⅰ on the production of exsome.Methods:Serum exosomes were extracted by PEG precipitation from 32 patients with gastric cancer and 26 healthy volunteers.Nanosight Tracking Analysis（NTA）was used to analyze exosomes,and chemiluminescence was used to detect serum tumor markers in patients with gastric cancer.Receiver operating characteristic（ROC）was used to analyze the predictive value of serum exosome size and concentration detection in gastric cancer staging.Ultrafast centrifugation method was used to extract the supernatant exosomes from MKN-28 gastric cancer cells,and NTA technique was used to detect and analyze the exosomes.The characteristics of exosomes Exo ^AHVAC-Ⅰsecreted by AHVAC-Ⅰ treated cells;The effects of Exo ^AHVAC-Ⅰon the migration ability of gastric cancer cell line MKN-28 were examined by scratch assay and Transwell chamber.Results:1)The serum Exosome particle size of 108.35±16.63nm in patients with gastric cancer was significantly lower than that of healthy control group（128.23±20.24nm）,Serum concentration of gastric cancer patients was 9.53±6.24（×107particals/ml）higher than that of healthy control group（6.14±3.43（×107particals/ml）.2）Serum Exosome particle size was negatively correlated with tumor pathological stage and clinical stage（P<0.05）.But there was no statistical difference between Exosome concentration and gastric cancer staging（P>0.05）.3)ROC analysis results showed that serum Exosome particle size had high confidence in the staging of gastric cancer（AUC=0.7579,P<0.05）.The combination of serum Exosome concentration,particle size and serum tumor markers in the assessment of gastric cancer pathological staging significantly improved the confidence（AUC=0.8452,P<0.01）.4)AHVAC-Ⅰ could significantly inhibit the production of Exosomes by gastric cancer cell line MKN-28 cells,and showed concentration dependent effect（P<0.05）.5)The number of transmembrane cells was significantly lower than that of the control group in the treatment of AHVAC-Ⅰtreated MKN-28 cells with Exosomes secreted by AHVAC-Ⅰtreated MKN-28 cells.6)MKN-28 cells secreted by AHVAC-Ⅰtreated MN-28 cells in Exosomes Exo ^AHVAC-Ⅰsignificantly decreased the repair ability of MKN-28 cells in the scratch area（P<0.05）.