NDLI: Iodide- and glucose-handling gene expression regulated by sorafenib or cabozantinib in papillary thyroid cancer.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dong, Qianggang Ruan, Maomei Chen, Libo Liu, Min
Description	Country affiliation: China Author Affiliation: Ruan M ( Department of Nuclear Medicine (M.R., M.L., L.C.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China)
Abstract	CONTEXT: The aberrant silencing of iodide-handling genes accompanied by up-regulation of glucose metabolism presents a major challenge for radioiodine treatment of papillary thyroid cancer (PTC). OBJECTIVE: This study aimed to evaluate the effect of tyrosine kinase inhibitors on iodide-handling and glucose-handling gene expression in BHP 2-7 cells harboring RET/PTC1 rearrangement. MAIN OUTCOME MEASURES: In this in vitro study, the effects of sorafenib or cabozantinib on cell growth, cycles, and apoptosis were investigated by cell proliferation assay, cell cycle analysis, and Annexin V-FITC apoptosis assay, respectively. The effect of both agents on signal transduction pathways was evaluated using the Western blot. Quantitative real-time PCR, Western blot, immunofluorescence, and radioisotope uptake assays were used to assess iodide-handling and glucose-handling gene expression. RESULTS: Both compounds inhibited cell proliferation in a time-dependent and dose-dependent manner and caused cell cycle arrest in the G0/G1 phase. Sorafenib blocked RET, AKT, and ERK1/2 phosphorylation, whereas cabozantinib blocked RET and AKT phosphorylation. The restoration of iodide-handling gene expression and inhibition of glucose transporter 1 and 3 expression could be induced by either drug. The robust expression of sodium/iodide symporter induced by either agent was confirmed, and (125)I uptake was correspondingly enhanced. (18)F-fluorodeoxyglucose accumulation was significantly decreased after treatment by either sorafenib or cabozantinib. CONCLUSIONS: Sorafenib and cabozantinib had marked effects on cell proliferation, cell cycle arrest, and signal transduction pathways in PTC cells harboring RET/PTC1 rearrangement. Both agents could be potentially used to enhance the expression of iodide-handling genes and inhibit the expression of glucose transporter genes.
ISSN	0021972X
e-ISSN	19457197
Journal	The Journal of Clinical Endocrinology & Metabolism
Issue Number	5
Volume Number	100
Language	English
Publisher	Oxford University Press
Publisher Date	2015-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Anilides Pharmacology Antineoplastic Agents Carcinoma, Papillary Genetics Gene Expression Regulation, Neoplastic Drug Effects Niacinamide Analogs & Derivatives Phenylurea Compounds Protein Kinase Inhibitors Pyridines Thyroid Neoplasms Therapeutic Use Apoptosis Autoantigens Drug Therapy Pathology Cell Cycle Cell Line, Tumor Cell Proliferation Glucose Transporter Type 1 Glucose Transporter Type 3 Iodide Peroxidase Iron-binding Proteins Microfilament Proteins Muscle Proteins Phosphorylation Proto-oncogene Proteins C-akt Proto-oncogene Proteins C-ret Receptors, Thyrotropin Signal Transduction Symporters Research Support, Non-u.s. Gov't Discipline Endocrinology Discipline Metabolism
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Endocrinology

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