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

被引：163

作者：

Chen, Guofang ^{[1
]}

Xu, Shuhang ^{[1
]}

Renko, Kostja ^{[2
]}

Derwahl, Michael ^{[1
]}

机构：

[1] St Hedwig Hosp, Dept Med, Div Endocrinol, D-10115 Berlin, Germany

[2] Univ Med, Charite, Inst Expt Endocrinol, D-10115 Berlin, Germany

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2012年 / 97卷 / 04期

关键词：

BREAST-CANCER; INSULIN-RESISTANCE; DIABETIC-PATIENTS; PROLIFERATION; MORTALITY; APOPTOSIS;

D O I：

10.1210/jc.2011-1754

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (J Clin Endocrinol Metab 97: E510-E520, 2012)

引用

页码：E510 / E520

页数：11

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