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

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Upregulation of glucose transporter 1 (GLUT1) and increased glycolysis are observed in less differentiated thyroid cancer.
• The therapeutic potential of targeting GLUT1 in thyroid cancer remains unclear.

Purpose of the Study:

• To investigate the efficacy of GLUT1 inhibitors as a therapeutic strategy for thyroid cancer.
• To evaluate the effects of GLUT1 inhibition on thyroid cancer cell growth, proliferation, cell cycle, and invasion.

Main Methods:

• Thyroid cancer cell lines were treated with two GLUT1 inhibitors: STF-31 and BAY-876.
• Functional assays were performed to assess cell growth, clonogenicity, cell cycle progression, autophagy activation, and invasiveness.
• Synergistic effects with lenvatinib were evaluated.

Main Results:

• GLUT1 inhibitors significantly reduced thyroid cancer cell growth and clonogenicity in a dose-dependent manner.
• Inhibitors induced G2/M cell cycle arrest and activated autophagy, without causing significant apoptosis.
• Suppression of cell invasiveness was observed in Transwell and spheroid models, with synergistic effects when combined with lenvatinib.

Conclusions:

• Targeting GLUT1 with inhibitors like STF-31 and BAY-876 shows promise for thyroid cancer therapy.
• GLUT1 inhibition leads to autophagy activation and cell cycle arrest, reducing tumor cell proliferation and invasion.
• Combination therapy with lenvatinib may enhance the efficacy of GLUT1 inhibitors in treating thyroid cancer.