Expression of GPX2 in intrahepatic cholangiocarcinoma and its effect on progression
10.19405/j.cnki.issn1000-1492.2024.08.007
- VernacularTitle:GPX2在肝内胆管癌中的表达及对其进展的影响
- Author:
Jianbo HE
1
;
Beicheng SUN
Author Information
1. 南京大学医学院附属鼓楼医院肝胆外科,南京 210008
- Keywords:
intrahepatic cholangiocarcinoma;
GPX2;
proliferation;
apoptosis;
epithelial-mesenchymal transition
- From:
Acta Universitatis Medicinalis Anhui
2024;59(8):1330-1338
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of Glutathione peroxidase 2(GPX2)in the occurrence and progres-sion of intrahepatic cholangiocarcinoma(ICC).Methods The Omicshare website was used to analyze GPX2 ex-pression levels in ICC.The expression levels in ICC were validated using quantitative real-time reverse transcription PCR(RT-qPCR),Western blot,and immunohistochemistry.Stable GPX2 knockdown and overexpression HuC-CT1 cell lines were constructed.The effects of GPX2 on ICC cell proliferation,migration,apoptosis,and epithelial-mesenchymal transition(EMT)were investigated using colony formation assays,cell counting kit-8(CCK-8)as-says,wound healing assays,Transwell assays,and flow cytometry.A mouse model of cholangiocarcinoma was con-structed to assess GPX2 expression in mouse cholangiocarcinoma tissues.Results Based on the analysis results from the Omicshare website,GPX2 was generally upregulated in intrahepatic cholangiocarcinoma(ICC)(P＜0.001).Western blot(P＜0.000 1),RT-qPCR(P＜0.001),and immunohistochemistry experiments showed that,compared to adjacent non-cancerous tissues,the expression of GPX2 was significantly elevated in ICC.When GPX2 was knocked down,the colony formation rate of cells decreased significantly(P＜0.01),and the prolifera-tion capacity was reduced(P＜0.001).Conversely,overexpression of GPX2 led to a significant increase in colony formation rate(P＜0.01)and enhanced proliferation capacity(P＜0.01).Results from wound healing and Tran-swell assays demonstrated that GPX2 knockdown slowed down cell wound healing(P＜0.01)and reduced migra-tion ability(P＜0.01).Additionally,GPX2 knockdown resulted in an increase in E-cadherin(P＜0.01)and a decrease in N-cadherin(P＜0.01)and Vimentin(P＜0.05).On the other hand,overexpression of GPX2 accel-erated wound healing(P＜0.05)and enhanced migration ability(P＜0.05),while E-cadherin expression de-creased(P＜0.05)and N-cadherin(P＜0.01)and Vimentin(P＜0.001)expression increased.Flow cytometry for apoptosis and Western blot experiments indicated that GPX2 knockdown increased the apoptosis rate(P＜0.001),decreased the expression of Bcl-2(P＜0.001),and increased the expression of BAX(P＜0.01).But overexpression of GPX2 reduced the apoptosis rate(P＜0.01),increased Bcl-2 expression(P＜0.000 1),and decreased BAX expression(P＜0.001).Finally,elevated levels of GPX2 were observed in a mouse model of cholangiocarcinoma.Conclusion GPX2 is highly expressed in human and mouse cholangiocarcinoma tissues,and it may enhance cholangiocarcinoma cell proliferation and migration,promote tumor cell EMT,and inhibit tumor cell apoptosis.
- Full text:2024091411482575782GPX2在肝内胆管癌中的表达及对其进展的影响_贺建波.pdf
