Effects of glabridin on proliferation,apoptosis,invasion,and migration of esophageal cancer cells by regulating JAK2/STAT3 signaling pathway
Objective To investigate the effects of glabridin(GLA)on the proliferation,apoptosis,invasion,and migration of esophageal cancer cells and analyze whether it is related to the regulation of the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods MTT assay was used to detect the cell survival rates of GLA intervention at 0,10,20,40,80,160,and 320 μmol·L-1,and IC50 was calculated.80,40,and 20 μmol·L-1 were determined as the doses for subsequent experiments in the GLA group,and control group,GLA(80 μmol·L-1)+Colivelin(0.5 μmol·L-1,JAK2/STAT3 pathway activator)group,GLA(80 μmol·L-1)+baricitini(10 μmol·L-1,JAK2 inhibitor)group were set up.CCK8 method was applied to detect cell viability,colony formation experiment was applied to detect cell cloning ability,transwell experiment was applied to detect cell invasion,the wound healing experiment was applied to detect cell migration,and immunoblotting was applied to detect the JAK2/STAT3 pathway and the expression of proliferation and migration proteins.A nude mouse model of esophageal cancer was established and randomly separated into a model group and a GLA(50 mg·kg-1)group.Administer ig once a day,euthanize mice after three weeks of treatment,analyze tumor mass and volume,and perform immunohistochemical staining to analyze JAK2 and STAT3 positive expression in tissues.Results Compared with the control group,the apoptosis rate of the GLA group increased,while the cell viability,cell clone number,invasion number,and migration rate decreased(P＜0.05).Compared with the GLA 80 μmol·L-1 group,the cell viability,number of cell clones,number of invasions,and migration rate in GLA+Colivelin group increased,while the apoptosis rate decreased(P＜0.05),the apoptosis rate of cells in the GLA+baricitinib group increased,while the vitality,number of cell clones,number of invasions,and migration rate decreased(P＜0.05).Compared with control group,the expression of Bax in cells of the GLA group increased,while the expression of p-JAK2,p-STAT3,c-MYC,Ki67,and MMP-9 decreased(P＜0.05).Compared with the GLA 80 μmol·L-1 group,the expression of p-JAK2,p-STAT3,c-MYC,Ki67,and MMP-9 in the GLA+Colivelin group increased,while the expression of Bax decreased(P＜0.05);the expression of Bax in the GLA+baricitinib group increased,while the expression of p-JAK2,p-STAT3,c-MYC,Ki67,and MMP-9 decreased(P＜0.05).Compared with the nude mice in model group,the tumor mass and volume in the GLA group decreased(P＜0.05),and the positive expression rates of JAK2 and STAT3 in the GLA group decreased(P＜0.05).Conclusion GLA can inhibit the JAK2/STAT3 pathway,thereby inhibiting the proliferation,invasion,migration,and promoting apoptosis of esophageal cancer cells.
glabridinJanus kinase 2/signal transducer and activator of transcription 3 pathwayesophageal cancerapoptosismigration
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