Abstract
Small cell lung cancer (SCLC), a highly angiogenic tumor, displays a 90% association with smoking. Nicotine promotes angiogenesis in lung cancer via alpha‐7‐nicotinic acetylcholine receptors (α7nAChRs). Therefore, α7nAChR antagonists should attenuate nicotine‐induced angiogenesis and be useful for the therapy of SCLC. Here we show that the α7nAChR antagonist MG624 suppresses proliferation of human microvascular endothelial cells from the lung (HMEC‐L) in response to nicotine. MG624 displays potent anti‐angiogenic activity in the Matrigel, rat aortic ring and chicken chorioallantoic membrane models. MG624 also inhibited nicotine‐induced angiogenesis in human SCLC tumors xenografted in athymic mice. The administration of MG624 did not cause any discomfort or lethargy in mice. Chromatin immunprecipitation assays show that MG624 decreases the recruitment of Egr‐1 on FGF2 promoter thereby decreasing its transcription and suppressing nicotine‐induced angiogenesis. Our results suggest that anti‐angiogenic agents like MG624 may be useful for the therapy of human SCLC.
Published Version
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