title: 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.
abstract: BACKGROUND
  Rab25, a member of Rab family of small guanosine triphosphatase, is associated with progression of various types of human cancers, including lung cancer, the leading cause of cancer-associated deaths around the globe.
  
  
  METHODS
  In this study, we report the gene therapeutic effect of short hairpin Rab25 RNA (shRab25) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in female A/J mice. Initially, mice (6 weeks old) were injected with single dose of NNK (2 mg/0.1 mL saline/mouse) by intraperitoneal injection to induce the tumor. Eight weeks later, shRab25 was complexed with glycerol propoxylate triacrylate-spermine (GPT-SPE) copolymer and delivered into tobacco-induced lung cancer models through a nose-only inhalation system twice a week for 2 months.
  
  
  RESULTS
  GPT-SPE/shRab25 largely decreased the tobacco-induced tumor numbers and tumor volume in the lungs compared to GPT-SPE- or GPT-SPE/shScr-delivered groups. Remarkably, aerosol-delivered GPT-SPE/shRab25 significantly decreased the expression level of Rab25 and other prominent apoptosis-related proteins in female A/J mice. The apoptosis in these mice was determined by detecting the expression level of Bcl-2, proliferating cell nuclear antigen, Bax, and further confirmed by TUNEL assay.
  
  
  CONCLUSIONS
  Our results strongly confirm the tumorigenic role of Rab25 in tobacco carcinogen-induced lung cancer and hence demonstrate aerosol delivery of shRab25 as a therapeutic target for lung cancer treatment.
authors: 1 Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research and The Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University , Seoul 151-742, Republic of Korea.
authors: Nomundelger
authors: N
authors: Gankhuyag
authors: 1 Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research and The Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University , Seoul 151-742, Republic of Korea.
authors: Kyeong Nam
authors: KN
authors: Yu
authors: 1 Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research and The Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University , Seoul 151-742, Republic of Korea.
authors: Orkhonselenge
authors: O
authors: Davaadamdin
authors: 1 Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research and The Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University , Seoul 151-742, Republic of Korea.
authors: Somin
authors: S
authors: Lee
authors: 1 Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research and The Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University , Seoul 151-742, Republic of Korea.
authors: Won Young
authors: WY
authors: Cho
authors: 2 Laboratory of Pathology, College of Veterinary Medicine, Seoul National University , Seoul, Korea.
authors: Changhoon
authors: C
authors: Park
authors: 3 State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University , Nanjing, China .
authors: Hu-Lin
authors: HL
authors: Jiang
authors: 4 Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University , Seoul, Korea.
authors: Bijay
authors: B
authors: Singh
authors: 2 Laboratory of Pathology, College of Veterinary Medicine, Seoul National University , Seoul, Korea.
authors: Chan-Hee
authors: CH
authors: Chae
authors: 1 Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research and The Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University , Seoul 151-742, Republic of Korea.
authors: Myung-Haing
authors: MH
authors: Cho
authors: 4 Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University , Seoul, Korea.
authors: Chong-Su
authors: CS
authors: Cho
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D002273:Carcinogens / Q000633:toxicity; D005260:Female; D005990:Glycerol / Q000737:chemistry; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D009602:Nitrosamines / Q000633:toxicity; D011506:Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D013096:Spermine / Q000008:administration & dosage*; D014026:Nicotiana / Q000633:toxicity; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D000336:Aerosols; D002273:Carcinogens; C426009:LAMTOR2 protein, mouse; D009602:Nitrosamines; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D013096:Spermine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D005990:Glycerol
keywords: A/J mice; NNK; aerosol-delivered shRab25; gene therapy; lung cancer