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Peptides. 2017 Mar;89:60-70. doi: 10.1016/j.peptides.2017.01.009. Epub 2017 Jan 24.
2
Expression of Receptors for Pituitary-Type Growth Hormone-Releasing Hormone (pGHRH-R) in Human Papillary Thyroid Cancer Cells: Effects of GHRH Antagonists on Matrix Metalloproteinase-2.垂体型生长激素释放激素受体（pGHRH-R）在人甲状腺乳头状癌细胞中的表达：生长激素释放激素拮抗剂对基质金属蛋白酶-2的影响
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Cancer. 2012 Feb 1;118(3):670-80. doi: 10.1002/cncr.26291. Epub 2011 Jul 12.

生长激素释放激素（GHRH）拮抗剂对甲状腺癌的抑制作用。

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

机构信息

Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal.

Institute for Research and Innovation in Health (I3S), University of Porto, Porto, Portugal.

出版信息

Horm Cancer. 2017 Dec;8(5-6):314-324. doi: 10.1007/s12672-017-0307-4. Epub 2017 Sep 18.

DOI:10.1007/s12672-017-0307-4
PMID:28924876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10355857/
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.

摘要

生长激素释放激素（GHRH）是一种由下丘脑分泌的肽类激素，它调节垂体中生长激素（GH）的合成和分泌。下丘脑外的 GHRH 及其同源受体（GHRHR 和剪接变异体）通过刺激细胞增殖和防止细胞凋亡来发挥有丝分裂作用。已经证实，GHRH 拮抗剂抑制各种人类恶性肿瘤的生长、致瘤性和转移。在这项工作中，我们研究了两种新的 GHRH 拮抗剂 MIA602 和 MIA690 对甲状腺癌的影响。我们研究了 MIA602 和 MIA690 对体外培养的甲状腺癌细胞系和体内鸡胚绒毛尿囊膜（CAM）试验中甲状腺癌的影响。我们发现 GHRH 和 GHRH 受体的 mRNA 在甲状腺癌细胞系和甲状腺肿瘤标本中表达。免疫组织化学证实了 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其凋亡。在体内，拮抗剂抑制植入的甲状腺肿瘤的生长和血管生成。我们的结果表明，GHRH 表达可能在甲状腺癌的生长中起作用，并且 GHRH 拮抗剂可能成为甲状腺癌患者的一种治疗选择。