Repeated Aerosol Delivery of Carboxyl-terminal Modulator Protein Suppresses Tumor in the Lungs of K-rasLA1 Mice
Repeated Aerosol Delivery of Carboxyl-terminal Modulator Protein Suppresses Tumor in the Lungs of K-rasLA1 Mice
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DOI：
10.1164/rccm.200810-1553oc
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发表时间：
2009-06-15
影响因子：
24.7
通讯作者：
Cho, Myung-Haing
中科院分区：
文献类型：
--
作者：
Hwang, Soon-Kyung;Lim, Hwang-Tae;Cho, Myung-Haing
理论基础：用传统疗法治疗的肺癌患者难以获得长期生存，这表明需要新的治疗方法。近年来，气雾剂介导的基因传递技术的进展为肺癌的安全有效治疗提供了可能。目的：探讨羧基末端调节蛋白(CTMP)在多阶段肺癌发生中的重复作用。在这项研究中，我们通过研究基于慢病毒的CTMP在9周龄和13周龄的肺癌模型K-ras(LA1)小鼠肺部的作用来解决这个问题。方法：将基于慢病毒的CTMP气雾剂通过只鼻吸入系统每周两次输送到9周和13周龄的肺癌模型K-ras(LA1)小鼠体内，连续4周。评估了CTMP对肺癌进展和Akt相关信号的影响。测量和主要结果：长期重复给予CTMP有效地减少了不同发育阶段的肺部肿瘤的进展。慢病毒-CTMP可抑制9周龄K-ras(LA1)小鼠肺组织蛋白质合成和细胞周期，改变Akt信号转导途径，促进13周龄K-ras(LA1)小鼠肺组织细胞凋亡。结论：长期重复的CTMP病毒给药可为设计肺肿瘤治疗方案提供有用的工具。
Rationale: Difficulties in achieving long-term survival of patients with lung cancer treated with conventional therapies suggest that novel approaches are required. Recent advances in aerosol-mediated gene delivery have provided the possibility of an alternative for the safe and effective treatment of lung cancer.Objectives: To investigate the repeated effect of carboxyl-terminal modulator protein (CTMP) on multistage lung tumorigenesis. In this study, we addressed this question by studying the effects of lentivirus-based CTMP in the lungs of 9- and 13-week-old K-ras(LA1) mice, a model of lung cancer.Methods: An aerosol of lentivirus-based CTMP was delivered into 9- and 13-week-old K-ras(LA1) mice, a model of lung cancer, through a nose-only inhalation system twice a week for 4 weeks. The effects of CTMP on lung cancer progression and Akt-related signals were evaluated.Measurements and Main Results: Long-term repeated delivery of CTMP effectively reduced tumor progression in the lungs at different stages of development. Lentiviral-CTMP inhibited protein synthesis and cell cycle and altered Akt signaling pathway in the lungs of 9-week-old K-ras(LA1) mice, and increased apoptosis was observed in the lungs of 13-week-old K-ras(LA1) mice.Conclusions: Long-term repeated viral delivery of CTMP may provide a useful tool for designing lung tumor treatment.