期刊
ENDOCRINOLOGY
卷 152, 期 2, 页码 536-544出版社
ENDOCRINE SOC
DOI: 10.1210/en.2010-0642
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资金
- Ministry of Health & Welfare, Republic of Korea [A085136]
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. (Endocrinology 152: 536-544, 2011)
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