Abemaciclib (CDK4/6 Inhibitor) Blockade Induces Cytotoxicity in Human Anaplastic Thyroid Carcinoma Cells.

Background: Thyroid cancer is the most prevalent endocrine malignancies globally. Anaplastic thyroid carcinoma (ATC) accounts for 1-3% of all Thyroid cancer. The evidence showed that ATC is a highly invasive solid tumor with poor prognosis. Despite conventional chemotherapy treatments, a considerable number of patients show developing resistance to therapeutic agents and tumor relapse. The aim of this study was the investigation anti-tumor effect of Abemaciclib (novel targeted cancer therapy drug) on Anaplastic Thyroid carcinoma SW1736 and C643 cell lines.

Methods: SW1736 and C643 cell lines were treated by desire concentrations of Abemaciclib (0, 1, 2.5, 5, 10, and 20 μM) and cell viability was measured by MTT assay. Also, Anoikis resistance assay was conducted for non-adherent the cells in the exposure of Abemaciclib. The gene expression of apoptotic and anti-apoptotic genes was conducted by quantitative Real-time PCR.

Results: Abemaciclib at the concentration of 10 and 20 μM effectively reduced cell proliferation and growth of the ATC cells compared to the control (p=0.000). Furthermore, we showed that 10 and 20 μM doses of the Abemaciclib inhibited the non-adherent ATC cells which were resistant to Anoikis death significantly (p=0.001). Moreover, we demonstrated this targeted therapy significantly reduced anti-apoptotic gene expression levels (BCL2 and CMYC) (p<0.05) and increased apoptotic gene expressions such as P21 and BAX (p<0.05).

Conclusion: Our data suggested that Abemaciclib can be utilized as a novel therapeutic agent in ATC cancer. Further in vivo and in vitro investigations are needed to evaluate molecular and clinical mechanisms of Abemaciclib.