Wednesday March 11 2009
CEA
Inhibition of Non-neuronal Alpha7-Nicotinic Receptor for Lung Cancer Treatment.
Am J Respir Crit Care Med. (2009) 179 (12) :1141-1150
CEA
RATIONALE: Recent studies strongly suggest that the nicotinic acethylcholine 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. OBJECTIVES: We therefore proposed that the alpha7-nAChR antagonists might be considered as potential anticancer agents. METHODS: In order to a) check the correlation between alpha7-nAChR presence and alpha-CbT sensitivity, binding experiments were performed in different human "normal" cells, lung cancer cell lines and primary tumoral cells; b) demonstrate that alpha-CbT might be an "efficient adjuvant therapy" for NSCLC we expanded our previous observations to a panel of NSCLCs of different subtypes orthotopically grafted on NOD/SCID mice; c) gain insight into the mechanism of alpha-CbT-induced tumour reduction, the cells obtained after enzymatic digestion of tumours have been analyzed for pro-caspase 9, Bax, Bad and Bcl-XL protein; and d) evaluate Snail/E-cadherin expression to acquire information on chemoresistance of cancer cells to äCbT. MEASUREMENTS AND MAIN RESULTS: We report herein the results of an experimental strategy aimed at investigating the anti-tumor effects of a powerful alpha7-nAChR antagonist, the Alpha-Cobratoxin (alpha-CbT) in an in vivo setting set to mimic at best the clinical scenery of lung cancer; additionally a possible explanation of alpha-CbT selectivity towards cancer cells has been searched for. CONCLUSIONS: We report a prolonged survival of alpha-CbT-treated animals in our mouse model of NSCLC, which is most likely the result of multiple mechanisms, including different antiproliferative and antiangiogenic effects.
Inhibition of Non-neuronal Alpha7-Nicotinic Receptor for Lung Cancer Treatment. (2009) Paleari L, Negri E, Catassi A, Cilli M, Servent D, D'Angelillo R, Cesario A, Russo P. Am J Respir Crit Care Med. sous presse.