尿刊酸修饰的壳聚糖介导的PTEN通过气溶胶递送抑制K-ras(LA1)小鼠的肺癌发生。

Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-ras(LA1) mice.

作者信息

Jin H, Xu C-X, Kim H-W, Chung Y-S, Shin J-Y, Chang S-H, Park S-J, Lee E-S, Hwang S-K, Kwon J-T, Minai-Tehrani A, Woo M, Noh M-S, Youn H-J, Kim D-Y, Yoon B-I, Lee K-H, Kim T-H, Cho C-S, Cho M-H

机构信息

Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.

出版信息

Cancer Gene Ther. 2008 May;15(5):275-83. doi: 10.1038/sj.cgt.7701116. Epub 2008 Feb 22.

DOI:10.1038/sj.cgt.7701116

PMID:18292798

Abstract

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC-PTEN were delivered into K-ras(LA1) lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC-PTEN may be compatible with noninvasive in vivo gene therapy.

摘要

传统疗法在实现肺癌患者长期生存方面效率低下，这就需要开发新的治疗方案。重新审视气溶胶基因递送可能为肺癌的安全有效治疗提供一种替代方法。在本研究中，将前期研究设计的含咪唑环的尿刊酸修饰壳聚糖（UAC）用作基因载体。评估了第10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）对Akt相关信号和细胞周期调控的潜在影响。通过仅经鼻吸入系统，每周两次将UAC-PTEN气溶胶递送至K-ras(LA1)肺癌模型小鼠体内，共持续4周。递送的PTEN通过PTEN与p53之间形成核复合物，显著抑制肺肿瘤发展，同时抑制Akt相关信号以及细胞周期调控。总之，我们的结果表明，UAC-PTEN气溶胶递送可能与非侵入性体内基因治疗兼容。