The effects of hypoxic cholangiocarcinoma cell-derived exosome on the proliferation,migration,invasion,and JAK2/STAT3 signaling pathway
10.3969/j.issn.1673-9701.2025.24.007
- VernacularTitle:缺氧胆管癌细胞外泌体对增殖、迁移、侵袭及JAK2/STAT3通路的影响
- Author:
Jianhua ZHANG
1
;
Zijian SU
1
;
Jinhong LIAN
1
Author Information
1. 泉州市第一医院肝胆外科,福建泉州 362000
- Publication Type:Journal Article
- Keywords:
Hypoxia;
Cholangiocarcinoma;
Exosome;
Proliferation;
Migration;
Invasion;
Janus kinase 2/signal transducer and activator of transcription 3 pathway
- From:
China Modern Doctor
2025;63(24):29-34
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of exosome(Exo)secreted by cholangiocarcinoma(CCA)cells under hypoxic conditions on the proliferation,migration,invasion,and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway of CCA cells.Methods Exo secreted by CCA cells was extracted and identified.Exo under normoxic and hypoxic conditions were co-cultured with CCA cells and divided into normal oxygen group,hypoxic group,hypoxic+inhibitor group,and blank group.The proliferation,migration,and invasion abilities of CCA cells were tested separately.Immunoblotting was applied to detect the expression levels of relevant proteins.Results Exo carrying fluorescent dye 3,3'-dioctadecyloxacarbocyanine perchlorate was detected in CCA cytoplasm.Compared with blank group,the number of clone formation,cell migration and invasion cells in normoxic group increased,the expression of proliferating cell nuclear antigen(PCNA),matrix metallopeptidase(MMP)-2,MMP-9,neural cadherin(N-Cadherin),Vimentin,phosphorylated JAK2(p-JAK2)/JAK2,phosphorylated STAT3(p-STAT3)/STAT3 increased,and the expression of epithelial cadherin(E-Cadherin)decreased(P<0.05);Compared with normal oxygen group,the number of clone formation,cell migration and invasion cells in hypoxia group increased,the expression of PCNA,MMP-2,MMP-9,N-Cadherin,Vimentin,p-JAK2/JAK2 and p-STAT3/STAT3 increased,and the expression of E-Cadherin decreased(P<0.05).Compared with hypoxia group,the number of clone formation,cell migration and invasion cells in hypoxia+inhibitor group decreased,the expression of PCNA,MMP-2,MMP-9,N-Cadherin,Vimentin,p-JAK2/JAK2 and p-STAT3/STAT3 decreased,and the expression of E-Cadherin increased(P<0.05).Conclusion Exo secreted by CCA cells under hypoxic conditions promote proliferation,migration,invasion,and epithelial mesenchymal transition of CCA cell by activating the JAK2/STAT3 pathway.