SHP1/Src imbalance induced by oxidative stress promotes the invasion and growth of advanced adenocarcinoma of esophagogastric junction
Objective It is to investigate the effect of oxidative stress(OS)-induced imbalance of SH2 domain-contai-ning protein tyrosine phosphatase 1(SHP1)/tyrosine kinase(Src)on the invasion and growth of advanced adenocarcinoma of esophagogastric junction(AEG).Methods①One hundred cases of patients with AEG treated with surgery in People's Hospital of Ningxia Hui Autonomous Region from January 2020 to April 2023 were selected and divided into early AEG group and late AEG group according to TNM stage.The pathological morphology of cancer tissues was observed by HE stai-ning,the positive protein expression of phosphorylated Src(p-Src)in cancer tissues was detected by immunohistochemis-try,and the protein expressions of p-Src,NADPH oxidase 4(NOX4),and NADPH oxidase 2(NOX2)in cancer tissues were detected by Western blot assay.②Human AEG tumor cells were cultured in vitro,and their proliferation ability was detected by CCK-8 assay,their migration ability was detected by Transwell assay,and the protein expressions of p-SHP1,p-Src,phosphorylated signal transducer and activator of transcription 3(p-STAT3),phosphorylated RUNX family tran-scription factor 3(p RUNX3)and RUNX3 were detected by Western blot assay.Results Compared with the early AEG group,the cancer tissues in the advanced AEG group was with obvious ischemia-hypoxia necrosis,and the positive expres-sion rate of p-Src protein and the relative expressions of p-Src,NOX2 and NOX4 proteins in the cancer tissues were signifi-cantly increased(all P<0.05).In the in vitro experiments,compared with the control group,the optical density value of cells cultured for 72 h in the NAC group was significantly decreased(P<0.05),the number of migrated cells was signifi-cantly reduced(P<0.05),the relative expressions of p-SHP1 and RUNX3 proteins in the cells were significantly in-creased(all P<0.05),and the relative expressions of p-Src,p-STAT3 and p-RUNX3 proteins in the cells were signifi-cantly decreased(all P<0.05);in the H2O2 group,the optical density value of cells cultured for 72 h was significantly increased(P<0.05),the number of migrated cells was significantly increased(P<0.05),the relative expressions of p-SHP1 and RUNX3 proteins in the cells were significantly decreased(all P<0.05),and the relative expressions of p-Src,p-STAT3 and p-RUNX3 proteins in the cells were all significantly increased(all P<0.05).Compared with the H2O2 group,the optical density values of cells cultured for 72 h were significantly decreased(all P<0.05),the numbers of mi-grated cells were significantly reduced(all P<0.05),and the relative expressions of RUNX3 protein in the cells were sig-nificantly increased(all P<0.05),and the relative expressions of p-SHP1,p-Src,p-STAT3,p-RUNX3 proteins in the cells were all significantly reduced in the H2O2+NAC group,H2O2+dasatinib group,and H2O2+dasatinib+NAC group(all P<0.05).There were no significant differences in optical density value,number of migrated cells and relative ex-pressions of p-Src,p-STAT3,p-RUNX3,RUNX3 in the cells between the H2O2+dasatinib group,H2O2+dasatinib+NAC group(all P>0.05),but the relative expression of p-SHP1 protein in the H2O2+dasatinib+NAC group was signifi-cantly higher than that in the H2O2+dasatinib group(P<0.05).Conclusion OS-induced imbalance of SHP1/Src pro-motes the invasion and growth of late AEG.
adenocarcinoma of esophagogastric junctionoxidative stressSHP1Srcinvasion
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维普
