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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.
Highlights
Thyroid cancer is the most frequent endocrine neoplasia and its incidence has been increasing in the past few decades
We found that FTS reduced the number of live cells with an half-maximal inhibitory concentration (IC50) of 17 μM and Modified citrus pectin (MCP)
Our results show that mixture of FTS and MCP has a combination index (CI)
Summary
Thyroid cancer is the most frequent endocrine neoplasia and its incidence has been increasing in the past few decades. Most patients with thyroid cancer have a good outcome when treated with standard therapies, which are: surgery, chemotherapy, and radiotherapy.[1] The prognosis for those with resistant or recurrent disease is poor. The classification of thyroid cancers is done by their histopathological and clinical characteristics, from welldifferentiated to undifferentiated types.[2] Well-differentiated types include papillary and follicular thyroid carcinoma. They are more common and have a good prognosis. Anaplastic thyroid carcinomas are undifferentiated, extremely aggressive, less common and usually lethal.[3]
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