Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin-3 inhibitors

Abstract

Anaplastic Thyroid carcinoma is an extremely aggressive solid tumor that resists most treatments and is almost always fatal. Galectin-3 (Gal-3) is an important marker for thyroid carcinomas and a scaffold of the K-Ras protein. S-trans, transfarnesylthiosalicylic acid (FTS; Salirasib) is a Ras inhibitor that inhibits the active forms of Ras proteins. Modified citrus pectin (MCP) is a water-soluble citrus-fruit-derived polysaccharide fiber that specifically inhibits Gal-3. The aim of this study was to develop a novel drug combination designed to treat aggressive anaplastic thyroid carcinoma. Combined treatment with FTS and MCP inhibited anaplastic thyroid cells proliferation in vitro by inducing cell cycle arrest and increasing apoptosis rate. Immunoblot analysis revealed a significant decrease in Pan-Ras, K-Ras, Ras-GTP, p-ERK, p53, and Gal-3 expression levels and significant increase in p21 expression levels. In nude mice, treatment with FTS and MCP inhibited tumor growth. Levels of Gal-3, K-Ras-GTP, and p-ERK were significantly decreased. To conclude, our results suggest K-Ras and Gal-3 as potential targets in anaplastic thyroid tumors and herald a novel treatment for highly aggressive anaplastic thyroid carcinoma.