論文

査読有り 国際誌
2019年2月1日

The correlation of p22phox and chemosensitivity in EGFR-TKI resistant lung adenocarcinoma.

Oncotarget
  • Masayuki Kobayashi
  • ,
  • Ryoko Saito
  • ,
  • Yasuhiro Miki
  • ,
  • Ren Nanamiya
  • ,
  • Chihiro Inoue
  • ,
  • Jiro Abe
  • ,
  • Ikuro Sato
  • ,
  • Yoshinori Okada
  • ,
  • Hironobu Sasano

10
10
開始ページ
1119
終了ページ
1131
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.18632/oncotarget.26637

Background: Enhancing the chemosensitivity in the patients with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistant lung adenocarcinoma (LUAD) is pivotal in achieving their successful therapeutic outcome. We aimed to explore the mechanisms regarding the development of therapeutic resistance to chemotherapy in EGFR-TKI resistant LUAD. Methods: Microarray analysis lead to potential involvement of p22phox, which was abundantly expressed in the cell lines harboring EGFR-TKI resistance and chemoresistance, and was known to regulate several important chemoresistance-associated factors such as hypoxia inducible factor-1α (HIF-1α) and epithelial-mesenchymal transition (EMT). We compared the status of p22phox with that of chemoresistance, HIF-1α expression and EMT in LUAD cell lines. We immunolocalized p22phox in the specimens of lung cancer patients. Results: p22phox and HIF-1α mRNAs were significantly elevated in the cells harboring EMT and chemoresistance. p22phox knockdown enhanced chemosensitivity and reduced the expression of HIF-1α and EMT-associated factors. HIF-1α knockdown enhanced the chemosensitivity, while HIF-1α transfection induced EMT and chemoresistance in these cell lines. All LUAD patients with T790M mutation were associated with abundant p22phox immunoreactivity in carcinoma cells. Conclusions: The analysis of p22phox in lung carcinoma tissues could provide new insights into the selection of chemotherapy for the patients with EGFR-TKI resistant LUAD.

リンク情報
DOI
https://doi.org/10.18632/oncotarget.26637
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30800222
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383684
ID情報
  • DOI : 10.18632/oncotarget.26637
  • PubMed ID : 30800222
  • PubMed Central 記事ID : PMC6383684

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