Lung cancer chemoprevention with the prostacyclin analogue iloprost is the most promising approach to date for intercepting progression of premalignant lung lesions in former smokers. Previous preclinical studies of iloprost used oral delivery, but a study modeling delivery directly to the target organ was needed. In vivo and in vitro studies have identified gene expression changes following iloprost treatment, including increased e-cadherin and Ppargγ and decreased COX2 and vimentin. We used tumor counts and gene expression to demonstrate the effectiveness of intranasal delivery of iloprost in a murine model of premalignant adenomas. Intranasal delivery of iloprost reduced adenoma multiplicity 14 weeks after urethane exposure in FVB/N mice compared with untreated urethane controls. Intranasal iloprost reversed urethane-induced gene expression changes in tumors and whole lung. These results correspond to previous studies of oral iloprost and in vitro treatment of human bronchial epithelial cells. This study demonstrates that intranasal delivery of iloprost in a mouse model of lung premalignant lesions is effective chemoprevention. This will be an essential tool for exploring mechanisms and outcomes of iloprost chemoprevention, along with supporting ongoing clinical trials of inhaled iloprost chemoprevention. Prevention Relevance: Iloprost is a promising chemoprevention agent for lung cancer and this work describes a new delivery approach in vivo.

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鼻内伊洛前列素预防小鼠肺癌发生模型中的肿瘤

使用前列环素类似物伊洛前列素进行肺癌化学预防是迄今为止最有希望的方法，用于拦截前吸烟者的癌前肺部病变进展。伊洛前列素以前的临床前研究使用口服给药，但需要一项研究模拟直接向靶器官给药。体内和体外研究已经确定了伊洛前列素治疗后的基因表达变化，包括增加的 e-cadherin 和 Ppargγ 以及减少的 COX2 和波形蛋白。我们使用肿瘤计数和基因表达来证明伊洛前列素鼻内给药在小鼠癌前腺瘤模型中的有效性。与未处理的氨基甲酸乙酯对照相比，在 FVB/N 小鼠中，在氨基甲酸乙酯暴露后 14 周，伊洛前列素鼻内给药减少了腺瘤的多样性。鼻内伊洛前列素可逆转聚氨酯诱导的肿瘤和全肺基因表达变化。这些结果对应于先前关于口服伊洛前列素和体外人支气管上皮细胞治疗的研究。该研究表明，在肺癌前病变小鼠模型中鼻内给药伊洛前列素是有效的化学预防。这将成为探索伊洛前列素化学预防机制和结果的重要工具，同时支持正在进行的吸入伊洛前列素化学预防临床试验。预防相关性：伊洛前列素是一种很有前途的肺癌化学预防剂，这项工作描述了一种新的体内递送方法。该研究表明，在肺癌前病变小鼠模型中鼻内给药伊洛前列素是有效的化学预防。这将成为探索伊洛前列素化学预防机制和结果的重要工具，同时支持正在进行的吸入伊洛前列素化学预防临床试验。预防相关性：伊洛前列素是一种很有前途的肺癌化学预防剂，这项工作描述了一种新的体内递送方法。该研究表明，在肺癌前病变小鼠模型中鼻内给药伊洛前列素是有效的化学预防。这将成为探索伊洛前列素化学预防机制和结果的重要工具，同时支持正在进行的吸入伊洛前列素化学预防临床试验。预防相关性：伊洛前列素是一种很有前途的肺癌化学预防剂，这项工作描述了一种新的体内递送方法。