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Cited by 196Metabolism, Diabetes, and CancerThyroid Cancer Diagnosis and TreatmentCancer, Hypoxia, and Metabolism

The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.

Metformin Inhibits Growth of Thyroid Carcinoma Cells, Suppresses Self-Renewal of Derived Cancer Stem Cells, and Potentiates the Effect of Chemotherapeutic Agents

Chen, Guofang, Xu, Shuhang, Renko, Kostja, Derwahl, Michael·2012·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2011-1754
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Abstract

CONTEXT: Hyperinsulinemia and insulin resistance are the major reasons for a higher prevalence of several cancer entities in type 2 diabetes mellitus and obesity. Metformin exerts a growth-inhibitory effect by reducing hyperinsulinemia and by a direct cellular action. OBJECTIVE: We investigated the effect of metformin on growth of differentiated human thyroid cells, anaplastic thyroid carcinoma cells, a doxorubicin-resistant thyroid carcinoma cell line, and thyroid cancer stem cells. DESIGN: The antimitogenic effect of metformin was studied in thyroid cells derived from goiters and in thyroid carcinoma cell lines by analysis of cell growth, cell cycle progression, and apoptosis. Furthermore, the influence of pretreatment with insulin or with chemotherapeutic agents on metformin-induced growth inhibition was investigated in thyroid carcinoma cells, in a doxorubicin-resistant thyroid carcinoma cell line, and in derived carcinoma stem cells. RESULTS: Metformin showed an antimitogenic effect by inhibition of cell cycle progression and induction of apoptosis. In addition, metformin antagonized the growth-stimulatory effect of insulin, inhibited clonal cell growth, reduced thyroid cancer sphere formation, and potentiated the antimitogenic effect of chemotherapeutic agents such as doxorubicin and cisplatin on undifferentiated thyroid carcinoma cells. Remarkably, the antiproliferative effect of metformin was even found in a doxorubicin-resistant thyroid carcinoma cell line. The growth-inhibitory effect of metformin was, however, not restricted to differentiated thyroid cells and undifferentiated thyroid carcinoma cells but was also demonstrated in thyroid carcinoma cancer stem cells. CONCLUSIONS: Metformin markedly diminished growth stimulation by insulin and showed an additive antimitogenic effect to chemotherapeutics agents. Therefore, our results suggest this drug as adjuvant treatment for thyroid cancer in type 2 diabetic patients.

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Metadata

Authors
Chen, G., Xu, S., Renko, K., & Derwahl, M.
Affiliations
  • St. Hedwig-Krankenhaus (DE)
  • Charité – Universitätsmedizin Berlin (DE)
Corresponding author
Derwahl, Michael
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2012-04
Volume
97
Issue
4
Pages
E510-E520
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2011-1754
OpenAlex
W2124231104
Cited by
196
References
32
Citations by year
2026: 4 · 2025: 6 · 2024: 11 · 2023: 15 · 2022: 14 · 2021: 6 · 2020: 11 · 2019: 13 · 2018: 18 · 2017: 15 · 2016: 12 · 2015: 19 · 2014: 19 · 2013: 15 · 2012: 17
FWCI
8.98
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
Government of Jiangsu Province
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
metformin, thyroid cancer, cancer stem cells, self-renewal, doxorubicin resistance, cisplatin, chemosensitization, insulin resistance, hyperinsulinemia, type 2 diabetes, apoptosis, cell cycle arrest, cell growth inhibition, adjuvant therapy
MeSH terms
Animals, Antineoplastic Agents, Carcinoma, Cell Cycle, Cell Differentiation, Cell Line, Goiter, Nodular, Humans, Hypoglycemic Agents, Insulin, Insulin Antagonists, Metformin, Thyroid Neoplasms, Tumor Cells, Cultured, Neoplastic Stem Cells, Apoptosis, Adenocarcinoma, Follicular, Drug Resistance, Neoplasm, Cell Line, Tumor, Cell Proliferation, Rats, Thyroid Carcinoma, Anaplastic

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