Kanashiro Celia A, Schally Andrew V, Varga Jozsef L, Hammann Brian, Halmos Gabor, Zarandi Marta
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, 1601 Perdido Street, New Orleans, LA 70112, USA.
Cancer Lett. 2005 Aug 26;226(2):123-31. doi: 10.1016/j.canlet.2005.01.008.
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.
在人小细胞肺癌H-69细胞中，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的体内治疗对表皮生长因子受体（EGFR）家族的影响。通过逆转录聚合酶链反应（RT-PCR）、免疫印迹和结合试验对肿瘤进行分析。用这些类似物治疗使EGFR的结合能力降低了18%-64%，并分别抑制了EGFR、HER-2和HER-3的mRNA表达27%-75.4%、17%-26.3%和13.8%-46.6%。这些拮抗剂还使EGFR的蛋白水平降低了21%-34%，HER-2降低了36%-68%，HER-3降低了43%-49%。这首次证明了GHRH拮抗剂的抗增殖作用与EGF/HER受体的下调有关。
