[1]郑楠,袁继红,刘欣,等.甲状腺激素促进肿瘤细胞增殖及血管新生信号通路的研究[J].国际内分泌代谢杂志,2014,(03):149-152.[doi:10.3760/cma.j.issn.1673-4157.2014.03.002]
　Zheng Nan,Yuan Jihong,Liu Xin,et al.Signaling pathway of thyroid hormone on the promotion of tumor cell proliferation and angiogenesis[J].International Journal of Endocrinology and Metabolism,2014,(03):149-152.[doi:10.3760/cma.j.issn.1673-4157.2014.03.002]
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甲状腺激素促进肿瘤细胞增殖及血管新生信号通路的研究()
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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
期数:
2014年03期
页码:
149-152
栏目:
论著
出版日期:
2014-06-30

文章信息/Info

Title:
Signaling pathway of thyroid hormone on the promotion of tumor cell proliferation and angiogenesis
作者:
郑楠; 袁继红; 刘欣; 周晓丽; 胡志梅; 史亚男; 李兰英
300070　天津医科大学代谢病医院内分泌研究所,卫生部激素与发育重点实验室 　　
Author(s):
Zheng Nan; Yuan Jihong; Liu Xin; Zhou Xiaoli; Hu Zhimei; Shi Yanan; Li Lanying.
Key Laboratory of Hormones and Development,Ministry of Health,Institute of Endocrinology,The Metabolic Diseases Hospital, Tianjin Medical University,Tianjin 300070,China Corresponding author：Li Lanying,Email：lily@tijmu.edu.cn
关键词:
甲状腺激素; 血管内皮生长因子; 整合素?琢vβ3; 蛋白激酶C; 蛋白激酶D1; 组蛋白去乙酰化酶5
Keywords:
Thyroid hormone; Vascular endothelial growth factor; Integrin ?琢vβ3; Protein kinase C; Protein kinase D1; Histone deacetylase 5
DOI:
10.3760/cma.j.issn.1673-4157.2014.03.002
摘要:
目的　探讨甲状腺激素促进肿瘤细胞增殖及血管新生的信号通路。方法　体外培养人胶质母细胞瘤细胞系（SNB19）,给予甲状腺激素（主要为T4,100 nmol/L）、四碘甲腺乙酸（tetraiodothy-roacetic acid,Tetrac,100 nmol/L）、蛋白激酶C（PKC）抑制剂（2.5 ?滋mol/L）作用后,采用Western印迹方法检测磷酸化蛋白激酶D1（PKD1）、磷酸化组蛋白去乙酰化酶（HDAC）5、磷酸化细胞外信号调节激酶（ERK）1/2的表达,ELISA方法检测细胞培养上清血管内皮生长因子（VEGF）的表达量,3-（4,5）-2-唑噻-（2,5）-二苯基溴化四氮唑蓝（MTT）比色法检测细胞增殖。结果　与对照组相比,T4干预组磷酸化PKD1、磷酸化HDAC5、磷酸化ERK1/2水平均增加（P均＜0.05）,Tetrac干预组及PKC抑制剂干预组磷酸化PKD1、磷酸化HDAC5、磷酸化ERK1/2水平均降低（P均＜0.05）。ELISA结果显示,与对照组相比,T4干预组VEGF浓度升高[（56.763±2.611） ng/L vs.（36.597±0.933） ng/L,P ＜0.05],Tetrac+T4干预组VEGF浓度降低[（22.215±1.531） ng/L vs.（36.597±0.933） ng/L,P ＜0.05]。MTT结果显示,与对照组相比,T4干预组OD值较高[（0.333±0.020） vs.（0.243±0.006）,P ＜0.05],Tetrac干预组OD值较低[（0.060±0.016） vs.（0.243±0.006）,P ＜0.05]。结论　甲状腺激素通过结合整合素?琢vβ3,激活ERK1/2信号通路促进肿瘤细胞增殖,激活PKC/PKD1/HDAC5信号通路促进血管新生。
Abstract:
Objective　To study the signaling pathway of proliferation and angiogenesis of tumor cells promoted by thyroid hormone. Methods　Human glioblastoma cells（SNB19） were cultured with thyroid hormone （mainly T4,100 nmol/L）,tetraiodothyroacetic acid（Tetrac,100 nmol/L） or protein kinase C （PKC） inhibitor（2.5 ?滋mol/L） in vitro.The expression of phosphorylated protein kinase D1（PKD1）,phosphorylated histone deacetylase （HDAC）5 and phosphorylated extracellular regulated protein kinases（ERK）1/2 were detected by Western blots.The expression of vascular endothelial growth factor （VEGF） in supernatant was measured by ELISA. The proliferation of SNB19 cells was detected by 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） colorimetric method. Results　Compared with control group,phosphorylated PKD1,phosphory-lated HDAC5 and phosphorylated ERK1/2 were all increased in T4 group （all P ＜0.05）,and decreased in Tetrac+T4 group and PKC inhibitor group （all P ＜0.05）.The concentration of VEGF in T4 group was enhanced[（56.763±2.611） ng/L vs.（36.597±0.933） ng/L,P ＜0.05],while reduced in Tetrac+T4 group [（22.215±1.531） ng/L vs.（36.597±0.933） ng/L,P ＜0.05],compared with control group. The results of MTT showed that compared with control group,the OD value of T4 group was enhanced[（0.333±0.020） vs.（0.243±0.006）, P ＜0.05],and reduced in Tetrac+T4 group[（0.060±0.016） vs.（0.243±0.006）,P ＜0.05]. Conclusion　Through binding to membrane integrin ?琢vβ3, thyroid hormone promotes the proliferation of tumor cells by activating the ERK1/2 signaling pathway,and promotes angiogenesis by activating the PKC/PKD1/HDAC5 signaling pathway.

参考文献/References:

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备注/Memo

备注/Memo:
通信作者： 李兰英,Email：lily@tijmu.edu.cn
更新日期/Last Update: 2014-05-20