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Updated: Aug 8, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
The effects of Abemaciclib on cell cycle and apoptosis regulation in anaplastic thyroid cancer cells
Elaheh S Abutorabi1,2, Arash Poursheikhani3, Bahareh Kashani1
1Hematology/Oncology and Stem Cell Transplantation Research Center, School of Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Background:
Anaplastic thyroid cancer (ATC) is an aggressive subtype of thyroid cancer, accounting for 1 to 2% of all cases. Deregulations of cell cycle regulatory genes including cyclins, cyclin-dependent kinases (CDKs), and endogenous inhibitors of CDKs (CKIs) are hallmarks of cancer cells and hence, studies indicate the inhibition of CDK4/6 kinases and cell cycle progression as potent therapeutic strategies. In this study, we investigated the anti-tumor activity of Abemaciclib, a CDK4 and CDK6 inhibitor, in ATC cell lines.
Methods And Results:
The ATC cell lines C643 and SW1736 were selected to study the antiproliferative effects of Abemaciclib using a cell proliferation assay and crystal violet staining assay. Annexin V/PI staining and cell cycle analysis by flow cytometry were also performed to examine the effects on apoptosis induction and cell cycle arrest. Wound healing assay and zymography analysis examined the effects of the drug on invasive abilities of ATC cells and Western blot analyses were applied to further study the anti-tumor mechanism of Abemaciclib, in addition to combination treatment with alpelisib. Our data demonstrated that Abemaciclib significantly inhibited cell proliferation and increased cellular apoptosis and cell cycle arrest in ATC cell lines, while considerably reducing cell migration and colony formation. The mechanism seemed to involve the PI3K pathway.
Conclusion:
Our preclinical data highlight CDK4/6 as interesting therapeutic targets in ATC and suggest CDK4/6-blockade therapies as promising strategies in this malignancy.
Insights
Abemaciclib, a CDK4/6 inhibitor, demonstrated significant anti-tumor effects in anaplastic thyroid cancer (ATC) models. It reduced cell proliferation and migration while inducing apoptosis and cell cycle arrest, suggesting potential therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Anaplastic thyroid cancer (ATC) is a rare and aggressive cancer.
- Cell cycle dysregulation is a hallmark of ATC.
- Targeting cyclin-dependent kinases (CDKs) is a promising therapeutic approach.
Purpose of the Study:
- To investigate the anti-tumor activity of Abemaciclib, a CDK4/6 inhibitor, in ATC.
- To evaluate the effects of Abemaciclib on ATC cell proliferation, apoptosis, cell cycle, and invasion.
Main Methods:
- Abemaciclib's effects were studied in ATC cell lines (C643, SW1736).
- Assays included cell proliferation, crystal violet staining, Annexin V/PI staining, cell cycle analysis, wound healing, zymography, and Western blot.
- Combination treatment with alpelisib was also explored.
Main Results:
- Abemaciclib significantly inhibited ATC cell proliferation and colony formation.
- The drug induced apoptosis and cell cycle arrest in ATC cells.
- Abemaciclib reduced cell migration and invasion, potentially via the PI3K pathway.
Conclusions:
- CDK4/6 are viable therapeutic targets in anaplastic thyroid cancer.
- CDK4/6 blockade therapies show promise for treating ATC.
- Preclinical data support Abemaciclib as a potential treatment for ATC.
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