دورية أكاديمية

Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway.

التفاصيل البيبلوغرافية
العنوان: Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway.
المؤلفون: Zhan Y; Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China., Wang R; Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China., Huang C; Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China., Xu X; Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China., Xiao X; Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China., Wu L; Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China., Wei J; Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China., Long T; Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China., Gao C; Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China.
المصدر: Oncology reports [Oncol Rep] 2024 Aug; Vol. 52 (2). Date of Electronic Publication: 2024 Jun 28.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: D.A. Spandidos Country of Publication: Greece NLM ID: 9422756 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-2431 (Electronic) Linking ISSN: 1021335X NLM ISO Abbreviation: Oncol Rep Subsets: MEDLINE
أسماء مطبوعة: Publication: <2003->: Athens : D.A. Spandidos
Original Publication: [Athens, Greece] : National Hellenic Research Foundation, 1994-
مواضيع طبية MeSH: Bile Duct Neoplasms*/drug therapy , Bile Duct Neoplasms*/pathology , Bile Duct Neoplasms*/metabolism , Bile Duct Neoplasms*/genetics , Cell Proliferation*/drug effects , Cholangiocarcinoma*/drug therapy , Cholangiocarcinoma*/pathology , Cholangiocarcinoma*/metabolism , Cholangiocarcinoma*/genetics , Digitoxin*/pharmacology , Signal Transduction*/drug effects, Humans ; Antigens, CD/metabolism ; Antigens, CD/genetics ; beta-D-Galactoside alpha 2-6-Sialyltransferase/metabolism ; Cell Line, Tumor ; Cell Movement/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; NF-kappa B/metabolism ; Sialyltransferases/genetics ; Sialyltransferases/metabolism
مستخلص: Intrahepatic cholangiocarcinoma (ICC) is a type of liver cancer associated with poor prognosis and increased mortality; the limited treatment strategy highlights the urgent need for investigation. Traditional Chinese Medicine (TCM), used alone or in combination with other treatments, can enhance therapeutic efficacy, improve life quality of patients and extend overall survival. In total, two rounds of screening of a TCM library of 2,538 active compounds were conducted using a Cell Counting Kit‑8 assay and ICC cell lines. Cell proliferation and migration abilities were assessed through colony formation, 5‑ethynyl‑2'‑deoxyuridine, would healing and Transwell assays. The impact of digitoxin (DT) on signaling pathways was initially investigated using RNA sequencing and further validated using reverse transcription‑quantitative PCR, western blotting, lectin blotting and flow cytometry. ICC cells stably overexpressing ST6 β‑galactoside α‑2,6‑sialyltransferase 1 (ST6GAL1) were generated through lentiviral transfection. It was shown that DT emerged as a highly effective anti‑ICC candidate from two rounds high‑throughput library screening. DT could inhibit the proliferation and migration of ICC cells by suppressing NF‑κB activation and reducing nuclear phosphorylated‑NF‑κB levels, along with diminishing ST6GAL1 mRNA and protein expression. The aforementioned biological effects and signal pathways of DT could be counteracted by overexpressing ST6GAL1 in ICC cells. In conclusion, DT suppressed ICC cell proliferation and migration by targeting the NF‑κB/ST6GAL1 signaling axis. The findings of the present study indicated the promising therapeutic effects of DT in managing ICC, offering new avenues for treatment strategies.
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فهرسة مساهمة: Keywords: DT; ICC; NF‑κB; ST6GAL1; treatment
المشرفين على المادة: 0 (Antigens, CD)
EC 2.4.99.1 (beta-D-Galactoside alpha 2-6-Sialyltransferase)
E90NZP2L9U (Digitoxin)
0 (NF-kappa B)
EC 2.4.99.- (Sialyltransferases)
EC 2.4.99.1 (ST6GAL1 protein, human)
تواريخ الأحداث: Date Created: 20240628 Date Completed: 20240628 Latest Revision: 20240724
رمز التحديث: 20240725
مُعرف محوري في PubMed: PMC11229393
DOI: 10.3892/or.2024.8762
PMID: 38940341
قاعدة البيانات: MEDLINE
الوصف
تدمد:1791-2431
DOI:10.3892/or.2024.8762