Author of

• 18971

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  P1.02 - Biology/Pathology (ID 614)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 22549

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    P1.02-065 - Histone Deacetylase Inhibition Alters Stem Cell Phenotype in Gefitinib-Resistant Lung Cancer Cells with EGFR Mutation (ID 7401)

    09:30 - 09:30  |  Author(s): K. Takahashi
    • Abstract

    Background:
    Cancer stem cells (CSCs) are epigenetically altered by histone deacetylase (HDAC), resulting in chromatin condensation. We have reported that gefitinib-resistant-persisters (GRP) population within non-small cell lung cancer (NSCLC) cells possesses CSCs features. The purpose of this study is to examine the role of HDAC in the gefitinib-resistant lung CSC.
    
    Method:
    We used HDAC1, HDAC2, and HDAC5 as markers of chromatin compaction in GRP of EGFR-mutant NSCLC cells PC9 and HCC827. Gefitinib-resistant tumor (GRT) was established by obtaining the remaining tumor in PC9-injected NOG mice after two weeks of gefitinib treatment. Quantitative real-time PCR were performed to analyze gene expressions. immunofluorescence and fluorescence-immunohistochemistry were performed to analyze protein expressions in the NSCLC cell lines and in vivo biopsy specimens, respectively. HDAC inhibitor Trichostatin-A was used to study the impact on the sensitivity of GRP to gefitinib and the implication on the CSC features.
    
    Result:
    PC9-GRP and HCC827-GRP cells expressed high level of HDAC1, HDAC2, and HDAC5. GRT also showed upregulation of HDAC1 compared to naïve PC9 tumor. Inhibition of HDAC reduced CSC-related factors and, reduced sphere formation of GRP, and increased sensitivity to gefitinib. Specimens from lung cancer patients with acquired resistance to gefitinib displayed high expression of HDAC1.
    
    Conclusion:
    HDAC is implicated in the CSC phenotype and is involved in the resistance to EGFR-TKI in NSCLC. Inhition of HDAC could be considered to reverse acquired resistance of EGFR-mutant to EGFR-TKI that is mediated by CSC.