Preliminary study on ketone body metabolism in anaplastic thyroid cancer

Background: Anaplastic thyroid cancer (ATC) is characterized by high invasiveness and rapid progression and has a poor prognosis. The aim of this study was to investigate the role of ketone body metabolism in ATC and provide a novel approach for ATC treatment. Methods: Human ATC cell lines, including 8505C and CAL-62, were used as the research objects. Cell Counting Kit-8 and colony formation assays appraised cell proliferation. Flow cytometry was performed to evaluate the cell cycle and apoptosis. Wound healing and transwell assays verified the migration and invasion of cells. Furthermore, tumor xenograft models were established to investigate the therapeutic effect of ketogenic diet in vivo. Immunohistochemistry was used to quantify the expression level of Ki67, Bcl-2, and caspase-3 in tumor tissues. Importantly, autophagy analyses included fluorescence microscopy for the observation of monodansylcadaverine staining, western blotting, and tissue immunofluorescence to determine autophagic protein (LC3, Beclin1, and p62) expression. Results: Acetoacetate (AcAc) inhibited the proliferation, migration, and invasion of ATC cells (8505C and CAL-62) and induced cell cycle arrest. Ketogenic diet significantly inhibited tumor growth in vivo. AcAc markedly elevated the level of autophagy. Autophagy inhibitor weakened the extent to which AcAc hindered cell proliferation, migration, and invasion and blocked cell cycle. Conclusion: The study demonstrated that the ketone body metabolite AcAc inhibits the proliferation, migration, and invasion of ATC cells and induces cell cycle arrest by inducing autophagy. Ketogenic diet provides a new strategy for the treatment of ATC.