An Investigation of the Combined Administration of Cholesterol-Lowering Agents and Anti-Diabetic Drugs on Cell Migration Inhibition of Anaplastic Thyroid Cancer Cells

Human anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignant tumors. Patients with ATC have a poor prognosis with a mean survival time of 2-6 months due to an aggressiveness of proliferation and invasive and metastatic outgrowth. Surgery, radiotherapy, and chemotherapy are not helpful in improving the survival time and the life quality of such patients. Since ATC is refractory to the conventional therapies, a new remedy has to be considered and further developed. We are interested in a combined remedy of cholesterol-lowering agent lovastatin and peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand troglitazone for the cancer therapy. Although previous studies had indicated that both drugs display the anti-cancer effects, the outcomes in clinical trials were relatively ineffective. For the improvement of anti-cancer efficacy, they have, respectively, been tested to combine with other agents and the diverse outcomes are shown. In this proposed research, we will attempt to examine the effects of a combined administration of lovastatin with troglitazone at the plasma-achievable concentrations on ATC cells. And, our preliminary results of cell migration assay show that the combination drug treatment effectively inhibited cell migration of ATC cells. Moreover, the combination drug treatment repressed the tumor growth in mouse xenograft model. We will evaluate the effects of this combination drug treatment on cellular toxicity, cell morphology dynamics and epithelial-mesenchymal transition (EMT) in ATC cells. Moreover, we will further investigate the molecular mechanisms underlying the effects of this combination drug treatment on ATC cells. The significance of the proposed research would be the development of a novel approach and it might provide an idea of potent therapeutic strategy for people suffered from ATC.