Inhibitory Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) in Thyroid Cancer.

IF 3 4区医学 Q3 Biochemistry, Genetics and Molecular Biology Hormones & Cancer Pub Date : 2017-12-01 DOI:10.1007/s12672-017-0307-4

Helena Pópulo, Bruno Nunes, Cristina Sampaio, Rui Batista, Marta Teixeira Pinto, Tiago B Gaspar, Leandro Miranda-Alves, Ren-Zhi Cai, Xian Yang Zhang, Andrew V Schally, Manuel Sobrinho-Simões, Paula Soares

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引用次数: 12

Abstract

Growth hormone-releasing hormone (GHRH) is a peptide hormone secreted by the hypothalamus that regulates the synthesis and secretion of growth hormone (GH) in the pituitary. The extra-hypothalamic GHRH and its cognate receptors (GHRHR and splice variants) play a mitogenic role by stimulating cell proliferation and preventing apoptotic cell death. It is well established that GHRH antagonists inhibit the growth, tumorigenicity, and metastasis of various human malignancies. In this work, we studied the effect of two new GHRH antagonists, MIA602 and MIA690, on thyroid cancer. We studied the effect of MIA602 and MIA690 on thyroid cancer in vitro, using human thyroid cancer cell lines, and in vivo, using chicken embryo chorioallantoic membrane (CAM) assays. We found that mRNA for GHRH and GHRH receptor is expressed in thyroid cell lines and in samples of thyroid tumors. Immunohistochemistry confirmed the expression of GHRHR protein in specimens of thyroid tumor. We observed that GHRH antagonists inhibited the growth and increased apoptosis of thyroid cancer cells. In vivo, the antagonists inhibited growth and angiogenesis of engrafted thyroid tumors. Our results suggest that GHRH expression may play a role in growth of thyroid cancer and that GHRH antagonists can be a therapeutic option for thyroid cancer patients.

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生长激素释放激素拮抗剂在甲状腺癌中的抑制作用。

生长激素释放激素(GHRH)是下丘脑分泌的一种肽激素，调节垂体中生长激素(GH)的合成和分泌。下丘脑外GHRH及其同源受体(GHRHR和剪接变体)通过刺激细胞增殖和防止凋亡细胞死亡发挥有丝分裂作用。GHRH拮抗剂可以抑制各种人类恶性肿瘤的生长、致瘤性和转移，这一点已经得到了很好的证实。在这项工作中，我们研究了两种新的GHRH拮抗剂MIA602和MIA690对甲状腺癌的作用。我们在体外、人甲状腺癌细胞系和鸡胚绒毛尿囊膜(CAM)实验中分别研究了MIA602和MIA690对甲状腺癌的作用。我们发现GHRH和GHRH受体的mRNA在甲状腺细胞系和甲状腺肿瘤样本中表达。免疫组化证实了GHRHR蛋白在甲状腺肿瘤标本中的表达。我们观察到GHRH拮抗剂抑制甲状腺癌细胞的生长并增加细胞凋亡。在体内，拮抗剂抑制移植甲状腺肿瘤的生长和血管生成。我们的研究结果表明，GHRH表达可能在甲状腺癌的生长中发挥作用，GHRH拮抗剂可能是甲状腺癌患者的治疗选择。

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来源期刊

Hormones & Cancer ONCOLOGY-ENDOCRINOLOGY & METABOLISM

CiteScore

4.60

自引率

0.00%

发文量

期刊介绍： Hormones and Cancer is a unique multidisciplinary translational journal featuring basic science, pre-clinical, epidemiological, and clinical research papers. It covers all aspects of the interface of Endocrinology and Oncology. Thus, the journal covers two main areas of research: Endocrine tumors (benign & malignant tumors of hormone secreting endocrine organs) and the effects of hormones on any type of tumor. We welcome all types of studies related to these fields, but our particular attention is on translational aspects of research. In addition to basic, pre-clinical, and epidemiological studies, we encourage submission of clinical studies including those that comprise small series of tumors in rare endocrine neoplasias and/or negative or confirmatory results provided that they significantly enhance our understanding of endocrine aspects of oncology. The journal does not publish case studies.