title: Aerosol delivery of eukaryotic translation initiation factor 4E-binding protein 1 effectively suppresses lung tumorigenesis in K-rasLA1 mice.
abstract: Conventional radiotherapy or chemotherapy for the long-term survival of patients with lung cancer is still difficult for treatment in metastatic and advanced tumors. Therefore, the safe and effective approaches to the treatment of lung cancer are needed. In this study, the effect of delivered eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) on lung cancer progression was evaluated. Recombinant adeno-associated virus (rAAV)-M3/4E-BP1 was delivered into 6-week-old K-rasLA1 lung cancer model mice through a nose-only inhalation system twice a week for 4 weeks. Long-term repeated delivery of 4E-BP1 effectively reduced tumor progression in the lungs of K-rasLA1 mice. Reduction of eIF4E by overexpression of 4E-BP1 resulted in suppression of cap-dependent protein expression of basic fibroblast growth factor (bFGF or FGF-2) and vascular endothelial growth factor (VEGF). In addition, delivered 4E-BP1 inhibited the proliferation of lung cancer cells in K-rasLA1 mice model. Our results suggest that long-term repeated viral delivery of 4E-BP1 may provide a useful tool for designing lung cancer treatment.
authors: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors: S-H
authors: SH
authors: Chang
authors: J-E
authors: JE
authors: Kim
authors: J-H
authors: JH
authors: Lee
authors: A
authors: A
authors: Minai-Tehrani
authors: K
authors: K
authors: Han
authors: C
authors: C
authors: Chae
authors: Y-H
authors: YH
authors: Cho
authors: J-H
authors: JH
authors: Yun
authors: K
authors: K
authors: Park
authors: Y-S
authors: YS
authors: Kim
authors: M-H
authors: MH
authors: Cho
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000008:administration & dosage* / Q000235:genetics; D000336:Aerosols / Q000008:administration & dosage*; D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins; D000229:Dependovirus / Q000378:metabolism; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D011905:Genes, ras; D015316:Genetic Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D010750:Phosphoproteins / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000336:Aerosols; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins