The correlation of p22 phox and chemosensitivity in EGFR-TKI resistant lung adenocarcinoma

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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 p22 phox , 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 p22 phox with that of chemoresistance, HIF-1α expression and EMT in LUAD cell lines. We immunolocalized p22 phox in the specimens of lung cancer patients. Results: p22 phox and HIF-1α mRNAs were significantly elevated in the cells harboring EMT and chemoresistance. p22 phox 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 p22 phox immunoreactivity in carcinoma cells. Conclusions: The analysis of p22 phox in lung carcinoma tissues could provide new insights into the selection of chemotherapy for the patients with EGFR-TKI resistant LUAD.

Original languageEnglish
Pages (from-to)1119-1131
Number of pages13
Issue number10
Publication statusPublished - 2019 Feb 1


  • Chemoresistance
  • EGFR-TKI resistance
  • EMT
  • HIF-1α
  • P22 x


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