title: Therapeutic potential of metformin in papillary thyroid cancer in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea.
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
authors.forename: Ka Hee
authors.initials: KH
authors.lastname: Yi
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Kyoung
authors.initials: SK
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ye An
authors.initials: YA
authors.lastname: Kim
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University Graduate School of Medicine, Incheon, Republic of Korea.
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: djpark@snu.ac.kr.
authors.forename: Do Joon
authors.initials: DJ
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy*; D002291:Carcinoma, Papillary; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D015398:Signal Transduction / Q000187:drug effects; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D008687:Metformin
keywords: AMPK; Akt; Ectopic tumor; Metformin; Mouse; Papillary thyroid cancer (PTC)