Severance Hospital Integrative Research Institute for Cerebral & Cardiovascular Diseases and Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Endocrinology. 2011 Feb;152(2):536-44. doi: 10.1210/en.2010-0642. Epub 2010 Dec 8.
The interaction between the chemokine stromal cell-derived factor 1 and its receptor CXCR4 plays an important role in GH production and cell proliferation in normal and tumorous pituitary somatotrope cells. Therefore, the chemokine receptor CXCR4 could be an attractive target for antitumor drugs in patients with acromegaly. A synthetic antagonist of CXCR4, cyclic pentapeptide d-Arg3FC131 (c[Gly1-d-Tyr2-d-Arg3-Arg4-Nal5]) significantly inhibited GH production and proliferation of GH3 somatotrope tumor cells in vitro. It also induced apoptosis of GH3 cells through activation of the caspase-3 pathway. Systemic administration of d-Arg3FC131 inhibited the growth of GH3 cell xenografts in immunodeficient nude mice by inducing apoptosis and suppressing the proliferation of tumor cells. These results indicate that d-Arg3FC131 might have potential for the treatment of pituitary tumors producing excess GH in patients with acromegaly.
趋化因子基质细胞衍生因子 1 与其受体 CXCR4 之间的相互作用在正常和肿瘤性垂体生长激素细胞中的 GH 产生和细胞增殖中发挥重要作用。因此，趋化因子受体 CXCR4 可能成为肢端肥大症患者抗肿瘤药物的一个有吸引力的靶点。CXCR4 的一种合成拮抗剂，环五肽 d-Arg3FC131（c[Gly1-d-Tyr2-d-Arg3-Arg4-Nal5]），显著抑制 GH3 生长激素细胞瘤体外 GH 的产生和增殖。它还通过激活 caspase-3 途径诱导 GH3 细胞凋亡。系统给予 d-Arg3FC131 通过诱导凋亡和抑制肿瘤细胞增殖，抑制免疫缺陷裸鼠中 GH3 细胞异种移植物的生长。这些结果表明，d-Arg3FC131 可能具有治疗肢端肥大症患者产生过多 GH 的垂体肿瘤的潜力。
