2008年8月
Suppression of surfactant protein A by an epidermal growth factor receptor tyrosine kinase inhibitor exacerbates lung inflammation
CANCER SCIENCE
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- 巻
- 99
- 号
- 8
- 開始ページ
- 1679
- 終了ページ
- 1684
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/j.1349-7006.2008.00857.x
- 出版者・発行元
- WILEY-BLACKWELL
Interstitial lung disease (ILD) is reported as a serious adverse event in lung cancer patients treated with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). However, the mechanisms of ILD associated with gefitinib remain unknown. To address the molecular mechanisms of ILD-associated gefitinib, we determined the effect of gefitinib treatment on surfactant protein expression in vitro and in vivo. Gefitinib treatment suppressed surfactant protein (SP)-A expression in H441 human lung adenocarcinoma cells expressing SP-A, -B, -C and -D by inhibiting epidermal growth factor signal. Next, gefitinib (200 mg/kg) was given p.o. to the mice daily for 1 week. Daily administration of gefitinib gradually reduced SP-A level in the bronchoalveolar lavage fluid. When lipopolysaccharide (LPS) was instilled intratracheally to the mice pretreated with gefitinib for 1 week, lung inflammation by LPS was exacerbated and prolonged. This exacerbation of lung inflammation was rescued by intranasal administration of SP-A. These results demonstrated that pretreatment with gefitinib exacerbated LPS-induced lung inflammation by reducing SP-A expression in the lung. This study suggests that epidermal growth factor receptor tyrosine kinase inhibitor may reduce SP-A expression in the lungs of lung cancer patients and thus patients treated with epidermal growth factor receptor tyrosine kinase inhibitor may be susceptible to pathogens. (Cancer Sci 2008; 99: 1679-1684)
- リンク情報
- ID情報
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- DOI : 10.1111/j.1349-7006.2008.00857.x
- ISSN : 1347-9032
- PubMed ID : 18754883
- Web of Science ID : WOS:000258440600025