Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Cancer Gene Ther. 2013 Jun;20(6):331-5. doi: 10.1038/cgt.2013.24. Epub 2013 May 3.
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.
常规放疗或化疗对转移性和晚期肿瘤患者的长期生存仍然难以治疗。因此，需要安全有效的肺癌治疗方法。本研究评估了真核翻译起始因子 4E（eIF4E）结合蛋白 1（4E-BP1）对肺癌进展的影响。通过鼻内吸入系统每周两次将重组腺相关病毒（rAAV）-M3/4E-BP1 递送至 6 周龄 K-rasLA1 肺癌模型小鼠，共 4 周。4E-BP1 的长期重复递送可有效降低 K-rasLA1 小鼠肺部肿瘤的进展。通过过表达 4E-BP1 降低 eIF4E 导致碱性成纤维细胞生长因子（bFGF 或 FGF-2）和血管内皮生长因子（VEGF）的帽依赖性蛋白表达受到抑制。此外，递送至 4E-BP1 抑制了 K-rasLA1 小鼠模型中肺癌细胞的增殖。我们的结果表明，4E-BP1 的长期重复病毒递送可能为设计肺癌治疗提供有用的工具。
