title: Dual expression of shAkt1 and Pdcd4 suppresses lung tumorigenesis in K-rasLA1 mice.
abstract: OBJECTIVE
  Lung cancer has the highest mortality rate among cancers and current therapies are not efficient. Therefore, novel therapeutic methods are urgently needed. Here, we examined the effectiveness of simultaneous Akt1 inhibition and Pdcd4 over-expression using a dual expression system in suppressing tumorigenesis in K-ras(LA1) mice (a lung cancer model).
  
  
  METHODS
  An shRNA targeting Akt1 (shAkt1) and cDNA of programmed cell death protein 4 (Pdcd4) were inserted into a dual expression vector (shAkt1+Pdcd4). A sorbitol diacrylate-polyethylenimine (SDA-PEI) carrier was used because of low toxicity and high transfection efficiency. Aerosolized SDA-PEI/shAkt1+Pdcd4 complex was delivered to the mice twice a week for 4 weeks using a nose-only exposure inhalation chamber.
  
  
  RESULTS
  Simultaneous Akt1 inhibition and Pdcd4 over-expression synergistically induced potent antitumor effect. Analysis revealed significant reduction in lung tumor number.
  
  
  CONCLUSIONS
  Dual expression of shAkt1 and Pdcd4 effectively suppresses lung tumorigenesis.
authors: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Seong-Ho
authors: SH
authors: Hong
authors: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Jae-Ho
authors: JH
authors: Lee
authors: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, P.R. China.
authors: Hu-Lin
authors: HL
authors: Jiang
authors: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Ji-Eun
authors: JE
authors: Kim
authors: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Ah Young
authors: AY
authors: Lee
authors: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea Graduate Group of Tumor Biology, Seoul National University, Seoul, Republic of Korea.
authors: Sanghwa
authors: S
authors: Kim
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Chong-Su
authors: CS
authors: Cho
authors: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea Graduate school of Convergence Science and Technology, Seoul National University, Suwon, Republic of Korea Graduate Group of Tumor Biology, Seoul National University, Seoul, Republic of Korea Advanced Institute of Convergence Technology, Seoul National University, Suwon, Republic of Korea Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun, Ganghon-do, Republic of Korea mchotox@snu.ac.kr.
authors: Myung-Haing
authors: MH
authors: Cho
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000276:immunology; D063646:Carcinogenesis / Q000235:genetics; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D015689:Oncogene Protein p21(ras) / Q000235:genetics; D011094:Polyethyleneimine / Q000008:administration & dosage; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D051017:Apoptosis Regulatory Proteins; C498443:Pdcd4 protein, mouse; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D011094:Polyethyleneimine; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D015689:Oncogene Protein p21(ras)
keywords: Lung cancer; PDCD4; aerosol delivery; gene therapy; shAkt1; sorbitol diacrylate