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Article Open Access

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

  • Authors:
    • Yueping Zhan
    • Rong Wang
    • Chenjun Huang
    • Xuewen Xu
    • Xiao Xiao
    • Linlin Wu
    • Jiao Wei
    • Tian Long
    • Chunfang Gao
  • View Affiliations / Copyright

    Affiliations: Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China
    Copyright: © Zhan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 103
    |
    Published online on: June 25, 2024
       https://doi.org/10.3892/or.2024.8762
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Abstract

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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Copy and paste a formatted citation
Spandidos Publications style
Zhan Y, Wang R, Huang C, Xu X, Xiao X, Wu L, Wei J, Long T and Gao C: Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway. Oncol Rep 52: 103, 2024.
APA
Zhan, Y., Wang, R., Huang, C., Xu, X., Xiao, X., Wu, L. ... Gao, C. (2024). Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway. Oncology Reports, 52, 103. https://doi.org/10.3892/or.2024.8762
MLA
Zhan, Y., Wang, R., Huang, C., Xu, X., Xiao, X., Wu, L., Wei, J., Long, T., Gao, C."Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway". Oncology Reports 52.2 (2024): 103.
Chicago
Zhan, Y., Wang, R., Huang, C., Xu, X., Xiao, X., Wu, L., Wei, J., Long, T., Gao, C."Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway". Oncology Reports 52, no. 2 (2024): 103. https://doi.org/10.3892/or.2024.8762
Copy and paste a formatted citation
x
Spandidos Publications style
Zhan Y, Wang R, Huang C, Xu X, Xiao X, Wu L, Wei J, Long T and Gao C: Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway. Oncol Rep 52: 103, 2024.
APA
Zhan, Y., Wang, R., Huang, C., Xu, X., Xiao, X., Wu, L. ... Gao, C. (2024). Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway. Oncology Reports, 52, 103. https://doi.org/10.3892/or.2024.8762
MLA
Zhan, Y., Wang, R., Huang, C., Xu, X., Xiao, X., Wu, L., Wei, J., Long, T., Gao, C."Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway". Oncology Reports 52.2 (2024): 103.
Chicago
Zhan, Y., Wang, R., Huang, C., Xu, X., Xiao, X., Wu, L., Wei, J., Long, T., Gao, C."Digitoxin inhibits ICC cell properties via the NF‑κB/ST6GAL1 signaling pathway". Oncology Reports 52, no. 2 (2024): 103. https://doi.org/10.3892/or.2024.8762
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