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- Title
Inhibition of nonneuronal alpha7-nicotinic receptor for lung cancer treatment.
- Authors
Paleari L; Negri E; Catassi A; Cilli M; Servent D; D'Angelillo R; Cesario A; Russo P; Fini M; Paleari, Laura; Negri, Eva; Catassi, Alessia; Cilli, Michele; Servent, Denis; D'Angelillo, Rolando; Cesario, Alfredo; Russo, Patrizia; Fini, Massimo
- Abstract
<bold>Rationale: </bold>Studies strongly suggest that the nicotinic acetylcholine receptors for nicotine (nAChRs) play a significant role in lung cancer predisposition and natural history. The nAChR alpha7 subunit has been found to be pivotal in the control of nicotine-induced lung cancer development and in growth signal transduction induced by nicotine binding to nAChRs.<bold>Objectives: </bold>To investigate the anticancer effects of alpha7-nAChR antagonists.<bold>Methods: </bold>(1) To check the correlation between alpha7-nAChR presence and alpha-cobratoxin (alpha-CbT) sensitivity, binding experiments were performed in various normal human cells, lung cancer cell lines, and primary tumoral cells; (2) to demonstrate that alpha-CbT might be an efficient adjuvant therapy for non-small cell lung cancer (NSCLC) we expanded our previous observations to a panel of NSCLCs of various subtypes orthotopically grafted on nonobese diabetic/severe combined immunodeficient mice; (3) to gain insight into the mechanism of alpha-CbT-induced tumor reduction, the cells obtained after enzymatic digestion of tumors were analyzed for procaspase-9, Bax, Bad, and Bcl-X(L) protein; and (4) Snail/E-cadherin expression was evaluated to acquire information about the chemoresistance of cancer cells to alpha-CbT.<bold>Measurements and Main Results: </bold>We report herein the results of an experimental strategy aimed at investigating the antitumor effects of a powerful alpha7-nAChR antagonist, alpha-CbT, in an in vivo setting set to mimic the clinical setting of lung cancer; in addition, a possible explanation for alpha-CbT selectivity toward cancer cells is presented.<bold>Conclusions: </bold>We report the prolonged survival of alpha-CbT-treated animals in our mouse model of NSCLC, which is most likely the result of multiple mechanisms, including various antiproliferative and antiangiogenic effects.
- Publication
American Journal of Respiratory & Critical Care Medicine, 2009, Vol 179, Issue 12, p1141
- ISSN
1073-449X
- Publication type
journal article
- DOI
10.1164/rccm.200806-908OC