Schally Andrew V, Varga Jozsef L, Engel Jörg B
Veterans Affairs Medical Center, Miami, FL 33125, USA.
Nat Clin Pract Endocrinol Metab. 2008 Jan;4(1):33-43. doi: 10.1038/ncpendmet0677.
This article reviews the potential clinical uses of antagonists of growth-hormone-releasing hormone (GHRH) for tumor therapy. GHRH antagonists suppress the growth of various human cancer lines xenografted into nude mice; such tumors include breast, ovarian, endometrial and prostate cancers, lung cancers (small-cell lung carcinomas and non-small-cell lung carcinomas), renal, pancreatic, gastric and colorectal carcinomas, brain tumors (malignant gliomas), osteogenic sarcomas and non-Hodgkin's lymphomas. The antitumor effects of GHRH antagonists are exerted in part indirectly through the inhibition of the secretion of GH from the pituitary and the resulting reduction in the levels of hepatic insulin-like growth factor I (IGF-I). The main effects of the GHRH antagonists are, however, exerted directly on tumors. GHRH ligand is present in various human cancers and might function as an autocrine and/or paracrine growth factor. Pituitary-type GHRH receptors and their splice variants are also found in many human cancers. The inhibitory effects of GHRH antagonists seem to be due to the blockade of action of tumoral GHRH. Antagonists of GHRH can also suppress cancer growth by blocking production of IGF-I and/or IGF-II by the tumor. Further development of GHRH antagonists that are still-more potent should lead to potential therapeutic agents for various cancers.
本文综述了生长激素释放激素（GHRH）拮抗剂在肿瘤治疗中的潜在临床应用。GHRH拮抗剂可抑制移植到裸鼠体内的多种人类癌细胞系的生长；这些肿瘤包括乳腺癌、卵巢癌、子宫内膜癌和前列腺癌、肺癌（小细胞肺癌和非小细胞肺癌）、肾癌、胰腺癌、胃癌和结直肠癌、脑肿瘤（恶性胶质瘤）、骨肉瘤和非霍奇金淋巴瘤。GHRH拮抗剂的抗肿瘤作用部分是通过抑制垂体分泌生长激素（GH）以及由此导致的肝脏胰岛素样生长因子I（IGF-I）水平降低而间接发挥的。然而，GHRH拮抗剂的主要作用是直接作用于肿瘤。GHRH配体存在于多种人类癌症中，可能作为自分泌和/或旁分泌生长因子发挥作用。垂体型GHRH受体及其剪接变体也在许多人类癌症中被发现。GHRH拮抗剂的抑制作用似乎是由于阻断了肿瘤GHRH的作用。GHRH拮抗剂还可通过阻断肿瘤产生IGF-I和/或IGF-II来抑制癌症生长。进一步开发更有效的GHRH拮抗剂应能产生用于治疗各种癌症的潜在治疗药物。
