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Anti‐angiogenic activity of MG624, an α7‐nicotinic receptor antagonist in human small cell lung cancer
Author(s) -
Brown Kathleen C,
Lau Jamie K,
Witte Ted R,
Hardman W Elaine,
Luo Haitao,
Chen Yi C,
Dasgupta Piyali
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.792.7
Angiogenesis represents the rate‐limiting step in tumor progression. Nicotine, the addictive component of cigarettes, can promote angiogenesis in lung cancer via nicotinic acetylcholine receptors (nAChRs). We show that nicotine stimulates angiogenesis in human microvascular lung endothelial cells (HMEC‐Ls) via the α7‐nAChR subunit. We conjectured that α7‐nAChR antagonists should attenuate nicotine‐induced angiogenesis and be useful for the therapy of lung cancers. Our results show that the α7‐nAChR antagonist MG624 displays potent anti‐angiogenic activity in three distinct models ‐ the Matrigel, rat aortic ring and chicken chorioallantoic membrane model. MG624 also inhibited nicotine‐induced angiogenesis in human small cell lung cancer tumors xenografted in athymic mice. The anti‐angiogenic activity of MG624 was due to its ability to inhibit nicotine‐induced production of basic fibroblast growth factor (bFGF). However, MG624 had no effect on nicotine‐induced vascular endothelial growth factor levels. The over‐expression of Egr‐1 reversed the anti‐angiogenic activity of MG624. Our results suggest that MG624 inhibits angiogenesis of lung endothelial cells via inhibition of Egr‐1 and bFGF.