Antagonists of growth hormone releasing hormone and bombesin inhibit the expression of EGF/HER receptor family in H-69 small cell lung carcinoma

Antagonists of growth hormone releasing hormone and bombesin inhibit the expression of EGF/HER receptor family in H-69 small cell lung carcinoma
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DOI:
10.1016/j.canlet.2005.01.008
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发表时间:
2005-08-26
期刊:
影响因子:
9.7
通讯作者:
Zarandi, M
Zarandi, M
中科院分区:
医学1区
文献类型:
--
作者:
Kanashiro, CA;Schally, AV;Zarandi, M

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在H-69 SCLC中研究了生长激素释放激素(GHRH)拮抗剂JV-1-65和MZ-J-7-110以及蛙皮素/胃泌素释放肽拮抗剂RC-3940-II对EGF受体(EGFR)家族的体内治疗作用。通过RT-PCR、免疫印迹和结合测定分析肿瘤。用这些类似物处理使EGFR的结合能力降低18- 64%,并分别抑制EGFR、HER-2和HER-3的mRNA表达27- 75.4%、17- 26.3%和13.8- 46.6%。拮抗剂还使EGFR的蛋白水平降低21- 34%,HER-2降低36-68%,HER-3降低43- 49%。这是第一次证明GHRH拮抗剂的抗增殖作用与EGF/HER受体的下调有关。(C)2005爱思唯尔爱尔兰有限公司保留所有权利。
Effects of in vivo treatment with antagonists of growth hormone-releasing hormone (GHRH), JV-1-65 and MZ-J-7-110, and bombesin/gastrin-releasing peptide antagonist RC-3940-II, on the EGF receptor (EGFR) family, were investigated in H-69 SCLC. Tumors were analyzed by RT-PCR, immunoblotting and binding assays. Treatment with these analogs reduced the binding capacity of EGFR by 18-64%, and inhibited the mRNA expression for EGFR, HER-2 and -3 by 27-75.4, 17-26.3, and 13.8-46.6%, respectively. The antagonists also decreased the protein levels for EGFR by 21-34%, HER-2 by 36-68% and HER-3 by 43-49%. This is the first demonstration that antiproliferative effects of GHRH antagonists are associated with a downregulation of EGF/HER receptors. (C) 2005 Elsevier Ireland Ltd. All rights reserved.