Effects of growth hormone-releasing hormone and its agonistic and antagonistic analogs in cancer and non-cancerous cell lines
Effects of growth hormone-releasing hormone and its agonistic and antagonistic analogs in cancer and non-cancerous cell lines
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DOI：
10.3892/ijo_00000613
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发表时间：
2010-05-01
影响因子：
5.2
通讯作者：
Schally, Andrew V.
中科院分区：
文献类型：
--
作者：
Barabutis, Nektarios;Siejka, Agnieszka;Schally, Andrew V.
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。除了作为促生长激素的生理作用外。在不同组织和各种肿瘤中充当生长因子。在这项研究中，我们评估了 GHRH 及其受体在各种癌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的影响。细胞周期蛋白 D3、肿瘤抑制蛋白 p53 和羧基末端结合蛋白 (CtBP1) 我们的研究结果表明，GHRH 激动剂 JI-38 下调 wt-p53 并上调 PCNA 的表达 GHRH 还上调 CtBP1 蛋白表达，并且其拮抗剂在 LNCaP 前列腺癌细胞中下调 CtBP1 蛋白表达。 GHRH 及其激动剂 JI-38 上调 A549 非小细胞肺癌中增殖标志物细胞周期蛋白 D3 和 PCNA 的表达，而 GHRH 拮抗剂 MZ-5-156 下调其表达。我们的结果支持之前关于 GHRH 在癌症中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
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 cancel 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