Glucose Transporter 1 Inhibitors Induce Autophagy and Synergize With Lenvatinib in Thyroid Cancer Cells

Background: Less differentiated thyroid cancer may upregulate the expression of glucose transporter 1 (GLUT1) and increase glycolytic activity. However, it is uncertain whether GLUT1 can be used as a target for therapy. Methods: Thyroid cancer cell lines were treated with two different GLUT1 inhibitors, STF-31 and BAY-876. Functional assays were conducted to evaluate the effects of these inhibitors on cell biology. Results: GLUT1 inhibitors dose-dependently decreased cell growth and clonogenicity of thyroid cancer cells. Cell cycle analysis showed that these inhibitors caused G2/M arrest instead of apoptosis. Additionally, treatment with GLUT1 inhibitors led to the activation of autophagy. In both the Transwell and spheroid models, GLUT1 inhibitors significantly suppressed cell invasiveness. Moreover, GLUT1 inhibitors demonstrated synergistic interactions when combined with lenvatinib. Conclusions: Treatment with GLUT1 inhibitors activates autophagy and provokes cell cycle arrest, accompanied by a decrease in colony formation and invasive capacity in thyroid cancer cells.