Research Service (151), Veterans Affairs Medical Center, Miami, FL 33125, USA.
Int J Oncol. 2010 May;36(5):1285-9. doi: 10.3892/ijo_00000613.
The neuropeptide growth hormone-releasing hormone (GHRH) is secreted by the hypothalamus and upon the binding to the receptors for GHRH on the pituitary gland regulates the release of growth hormone. Substantial evidence indicate that GHRH, in addition to its physiological role as a hypophysiotrophic hormone, acts as a growth factor in diverse tissues and various tumors. In this study we evaluated the expression of GHRH and its receptors in a variety of cancer and non-cancerous cell lines and studied the effect of GHRH antagonists and agonists on the proliferative cell nuclear antigen, cyclin D3, tumor suppressor protein p53 and carboxyl-terminal-binding protein (CtBP1). Our findings show that GHRH agonist JI-38 downregulates wt-p53 and upregulates the expression of PCNA. GHRH also upregulates CtBP1 protein expression and its antagonists downregulate it in LNCaP prostate cancer cells. Furthermore, GHRH and its agonist JI-38 upregulates the expression of the proliferative markers cyclin D3 and PCNA in A549 non-small cell lung carcinoma and GHRH antagonist MZ-5-156 downregulates it. Our results support previous findings on the mitogenic role of GHRH in cancers and underline the importance of GHRH antagonists as anticancer agents.
神经肽生长激素释放激素（GHRH）由下丘脑分泌，与垂体上的 GHRH 受体结合后，调节生长激素的释放。大量证据表明，GHRH 除了作为促垂体激素的生理作用外，还作为生长因子在多种组织和各种肿瘤中发挥作用。在这项研究中，我们评估了 GHRH 及其受体在多种癌症和非癌细胞系中的表达，并研究了 GHRH 拮抗剂和激动剂对增殖细胞核抗原、细胞周期蛋白 D3、肿瘤抑制蛋白 p53 和羧基末端结合蛋白（CtBP1）的影响。我们的研究结果表明，GHRH 激动剂 JI-38 下调 wt-p53 的表达并上调增殖细胞核抗原的表达。GHRH 还上调 LNCaP 前列腺癌细胞中 CtBP1 蛋白的表达，其拮抗剂则下调 CtBP1 蛋白的表达。此外，GHRH 及其激动剂 JI-38 上调非小细胞肺癌 A549 中增殖标志物 cyclin D3 和 PCNA 的表达，而 GHRH 拮抗剂 MZ-5-156 则下调其表达。我们的结果支持了先前关于 GHRH 在癌症中的促有丝分裂作用的发现，并强调了 GHRH 拮抗剂作为抗癌药物的重要性。
