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

被引：18

作者：

Ppulo, Helena ^{[1
,2
]}

Nunes, Bruno ^{[1
,2
,3
]}

Sampaio, Cristina ^{[1
,2
]}

Batista, Rui ^{[1
,2
,4
]}

Pinto, Marta Teixeira ^{[1
,2
]}

Gaspar, Tiago B. ^{[1
,2
]}

Miranda-Alves, Leandro ^{[1
,2
]}

Cai, Ren-Zhi ^{[5
,6
,7
,8
]}

Zhang, Xian Yang ^{[5
,6
,7
,8
]}

Schally, Andrew V. ^{[5
,6
,7
,8
,9
,10
]}

Sobrinho-Simes, Manuel ^{[1
,2
,11
,12
]}

Soares, Paula ^{[1
,2
,11
]}

机构：

[1] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Oporto, Portugal

[2] Univ Porto, Inst Res & Innovat Hlth I3S, Oporto, Portugal

[3] Univ Fed Rio de Janeiro, Expt Endocrinol GPEEx Grp, Med Fac, Inst Biomed Sci & Postgrad Endocrinol, Rio De Janeiro, Brazil

[4] Univ Porto, Med Fac, Oporto, Portugal

[5] Vet Affairs Med Ctr Miami, Miami, FL USA

[6] Univ Miami, Sch Med, Dept Med, Sylvester Comprehens Canc Ctr,Div Endocrinol, Miami, FL USA

[7] Univ Miami, Sch Med, Dept Med, Sylvester Comprehens Canc Ctr,Div Hematol Oncol, Miami, FL USA

[8] Univ Miami, Sch Med, Interdisciplinary Stem Cell Inst, Miami, FL USA

[9] Univ Miami, Sch Med, Dept Pathol, Sylvester Comprehens Canc Ctr,Div Endocrinol, Miami, FL USA

[10] Univ Miami, Sch Med, Dept Pathol, Div Hematol Oncol,Sylvester Comprehens Canc Ctr, Miami, FL USA

[11] Univ Porto, Med Fac, Dept Pathol & Oncol, Oporto, Portugal

[12] Hosp Sao Joao, Dept Pathol, Oporto, Portugal

来源：

HORMONES & CANCER | 2017年 / 8卷 / 5-6期

关键词：

Thyroid cancer; Growth hormone-releasing hormone; GHRH antagonists; Hypothalamic hormone; mRNA for GHRH; mRNA for GHRH receptors; SPLICE VARIANTS; PROSTATE-CANCER; EXPRESSION; RECEPTOR; CELLS; INCREASES; KINASE; RAS;

D O I：

10.1007/s12672-017-0307-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：314 / 324

页数：11

共 26 条

[11] A correlation of endocrine and anticancer effects of some antagonists of GHRH
Magdolna Kovacs
Schally, Andrew V.
Florian Hohla
Rick, Ferenc G.
Eva Pozsgai
Luca Szalontay
Varga, Jozsef L.
Marta Zarandi
[J]. PEPTIDES, 2010, 31 (10) : 1839 - 1846
[12] Chronic expression of RET/PTC3 enhances basal and insulin-stimulated Pl3 kinase/AKT signaling and increases IRS-2 expression in FRTL-5 thyroid cells
Miyagi, E
Braga-Basaria, M
Hardy, E
Vasko, V
Burman, KD
Jhiang, S
Saji, M
Ringel, MD
[J]. MOLECULAR CARCINOGENESIS, 2004, 41 (02) : 98 - 107
[13] Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation
Qin, Yong Jie
Chan, Sun On
Chong, Kelvin Kam Lung
Li, Benjamin Fuk Loi
Ng, Tsz Kin
Yip, Yolanda Wong Ying
Chen, Haoyu
Zhang, Mingzhi
Block, Norman L.
Cheung, Herman S.
Schally, Andrew V.
Pang, Chi Pui
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (51) : 18303 - 18308
[14] Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing hormone receptors from human cancers
Rekasi, Z
Czompoly, T
Schally, AV
Halmos, G
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (19) : 10561 - 10566
[15] Antagonists of growth hormone-releasing hormone inhibit growth of androgen-independent prostate cancer through inactivation of ERK and Akt kinases
Rick, Ferenc G.
Schally, Andrew V.
Szalontay, Luca
Block, Norman L.
Szepeshazi, Karoly
Nadji, Mehrdad
Zarandi, Marta
Hohla, Florian
Buchholz, Stefan
Seitz, Stephan
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (05) : 1655 - 1660
[16] Antagonists of growth hormone-releasing hormone (GHRH) reduce prostate size in experimental benign prostatic hyperplasia
Rick, Ferenc G.
Schally, Andrew V.
Block, Norman L.
Nadji, Mehrdad
Szepeshazi, Karoly
Zarandi, Marta
Vidaurre, Irving
Perez, Roberto
Halmos, Gabor
Szalontay, Luca
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (09) : 3755 - 3760
[17] Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras
RodriguezViciana, P
Warne, PH
Khwaja, A
Marte, BM
Pappin, D
Das, P
Waterfield, MD
Ridley, A
Downward, J
[J]. CELL, 1997, 89 (03) : 457 - 467
[18] Antagonists of growth-hormone-releasing hormone: an emerging new therapy for cancer
Schally, Andrew V.
Varga, Jozsef L.
Engel, Joerg B.
[J]. NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM, 2008, 4 (01): : 33 - 43
[19] SCHALLY AV, 1965, P SOC EXP BIOL MED, V119, P208
[20] Antineoplastic Action of Growth Hormone-Releasing Hormone (GHRH) Antagonists
Siejka, Agnieszka
Lawnicka, Hanna
Melen-Mucha, Gabriela
Motylewska, Ewelina
Komorowski, Jan
Stepien, Henryk
[J]. RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY, 2012, 7 (01) : 56 - 63

← 1 2 3 →