Suppression of Tobacco Carcinogen-Induced Lung Tumorigenesis by Aerosol-Delivered Glycerol Propoxylate Triacrylate-Spermine Copolymer/Short Hairpin Rab25 RNA Complexes in Female A/J Mice.

摘要: Abstract Background: Rab25, a member of Rab family small guanosine triphosphatase, is associated with progression various types human cancers, including lung cancer, the leading cause cancer-associated deaths around globe. Methods: In this study, we report gene therapeutic effect short hairpin Rab25 RNA (shRab25) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced tumorigenesis in female A/J mice. Initially, mice (6 weeks old) were injected single dose NNK (2 mg/0.1 mL saline/mouse) by intraperitoneal injection to induce tumor. Eight later, shRab25 was complexed glycerol propoxylate triacrylate-spermine (GPT-SPE) copolymer and delivered into tobacco-induced cancer models through nose-only inhalation system twice week for 2 months. Results: GPT-SPE/shRab25 largely decreased tumor numbers volume lungs compared GPT-SPE- or GPT-SPE/shScr-delivered groups. Remarkably, aerosol-delivered GPT-SPE/shRab2...