Galectin-3 Inhibitors Suppress Anoikis Resistance and Invasive Capacity in Thyroid Cancer Cells

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Galectin-3 is recognized as a key histologic marker in thyroid cancer.
• The therapeutic potential of targeting galectin-3 using pharmacological lectin-based approaches requires further investigation.

Purpose of the Study:

• To evaluate the therapeutic efficacy of novel galectin-3 inhibitors, GB1107 and TD139, against thyroid cancer cells.
• To elucidate the underlying molecular mechanisms of action for these inhibitors.

Main Methods:

• Thyroid cancer cells were treated with varying concentrations of GB1107 and TD139.
• Cell viability, clonogenicity, apoptosis, cell cycle, anoikis resistance, migration, and invasion were assessed.
• Key signaling pathways, including AKT/β-catenin, and protein expression (MMP2) were analyzed.

Main Results:

• High-dose TD139 reduced thyroid cancer cell viability and clonogenicity, inducing apoptosis.
• Both GB1107 and TD139 inhibited cell coherence, counteracted anoikis resistance, and dose-dependently decreased migration and invasion.
• Treatment attenuated AKT phosphorylation and decreased β-catenin and MMP2 expression.

Conclusions:

• Novel galectin-3 inhibitors, GB1107 and TD139, effectively suppress thyroid cancer cell anoikis resistance, motility, and invasiveness.
• These effects are mediated, at least in part, through the AKT/β-catenin signaling pathway.
• Galectin-3 inhibitors hold promise for preclinical evaluation in preventing or treating metastatic thyroid cancer.