Archives of medical research · 2026
Pro-Tumorigenic Roles of Cyclin Dependent Kinase 2 and its Associated Cyclins in Cholangiocarcinoma Progression under High Glucose Condition.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Taebprakhon Cheerapinya, Sorin Supannika, Khawkhiaw Kullanat, Phoomak Chatchai, Seubwai Wunchana, Wongkham Sopit, Saengboonmee Charupong
Аннотация
BACKGROUND: Previous studies have shown that hyperglycemia upregulates cyclin-dependent kinase 2 (CDK2) and its cyclin partners, cyclin E and cyclin A, in cholangiocarcinoma (CCA). However, the effects of targeting these proteins in a hyperglycemic state are unclear.
AIM: This study aimed to investigate the therapeutic effects of inhibiting CDK2 and its cyclin partners under high-glucose conditions.
METHODS: CCA cells were cultured in normal glucose (NG) and high glucose (HG) conditions. Expression of CDK2 and the associated cyclins was analyzed using online public databases and verified by Western blot. Cell proliferation and cytotoxicity were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. CDK2 activity was inhibited using tagtociclib. Cyclin E and cyclin A expression was suppressed using siRNA. Molecular mechanisms were analyzed using flow cytometry and Western blot.
RESULTS: CDK2, cyclin E, and cyclin A were upregulated in CCA tissues and cells cultured in the HG condition compared with normal bile ducts. Tagtociclib significantly suppressed CCA cell growth, with HG cells being more sensitive than NG cells. Partial suppression of cyclin E and cyclin A expression minimally affected cell growth but significantly reduced the metastatic phenotypes of CCA cells by suppressing the epithelial-mesenchymal transition.
CONCLUSION: CCA cells with upregulated CDK2 and its cyclin partners in HG were more sensitive to tagtociclib at a higher dose. Cyclin E and cyclin A also regulated CCA metastasis by controlling epithelial-mesenchymal transition. Targeting CDK2 and its associated cyclins in CCA cells demonstrated therapeutic potential that requires further translational and clinical verification.
AIM: This study aimed to investigate the therapeutic effects of inhibiting CDK2 and its cyclin partners under high-glucose conditions.
METHODS: CCA cells were cultured in normal glucose (NG) and high glucose (HG) conditions. Expression of CDK2 and the associated cyclins was analyzed using online public databases and verified by Western blot. Cell proliferation and cytotoxicity were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. CDK2 activity was inhibited using tagtociclib. Cyclin E and cyclin A expression was suppressed using siRNA. Molecular mechanisms were analyzed using flow cytometry and Western blot.
RESULTS: CDK2, cyclin E, and cyclin A were upregulated in CCA tissues and cells cultured in the HG condition compared with normal bile ducts. Tagtociclib significantly suppressed CCA cell growth, with HG cells being more sensitive than NG cells. Partial suppression of cyclin E and cyclin A expression minimally affected cell growth but significantly reduced the metastatic phenotypes of CCA cells by suppressing the epithelial-mesenchymal transition.
CONCLUSION: CCA cells with upregulated CDK2 and its cyclin partners in HG were more sensitive to tagtociclib at a higher dose. Cyclin E and cyclin A also regulated CCA metastasis by controlling epithelial-mesenchymal transition. Targeting CDK2 and its associated cyclins in CCA cells demonstrated therapeutic potential that requires further translational and clinical verification.