Therapeutic potential of metformin in papillary thyroid cancer in vitro and in vivo
| Autor: | Sun Wook Cho, Ye An Kim, Ka Hee Yi, Sun Kyoung Han, Hyun Jin Sun, Do Joon Park, Young Joo Park, Byung-Chul Oh |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
endocrine system diseases Blotting Western Mice Nude Antineoplastic Agents Apoptosis Type 2 diabetes Biochemistry Mice Endocrinology In vivo Internal medicine medicine Animals Humans Viability assay Thyroid Neoplasms Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Cells Cultured business.industry Carcinoma nutritional and metabolic diseases AMPK medicine.disease Flow Cytometry Carcinoma Papillary Metformin Gene Expression Regulation Neoplastic Disease Models Animal Thyroid Cancer Papillary Cancer research Female business medicine.drug Signal Transduction |
| Zdroj: | Molecular and cellular endocrinology. 393(1-2) |
| ISSN: | 1872-8057 |
| Popis: | Metformin, an anti-diabetic drug used in type 2 diabetes treatment, is reported to have oncopreventive or therapeutic roles in several human cancers. The present study investigated the therapeutic potential of physiologic dose of metformin in PTC. Metformin inhibited PTC cell viability and increased cell apoptosis in various doses (0.5-20mM) in BCPAP and BHP10-3SC cells. Western blot analysis demonstrated that the p-AMPK/AMPK ratio increased with increased metformin treatment. The ectopic tumor experiment was performed using BHP10-3SC cells and athymic nude mice. Oral metformin treatment via drinking water significantly delayed tumor growth in both tumor development model and established tumor models. Necrotic area in tumors significantly increased with metformin treatment. Western blot analysis revealed an increase in p-AMPK/AMPK ratio and suppressions of mTOR and Akt expressions in metformin-treated mice compared to the results in mock-treated control mice. Our results indicate that a physiologic dose of metformin has anti-tumorigenic effects that result from activation of AMPK signaling and inhibition of Akt signaling. |
| Databáze: | OpenAIRE |
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