Author of

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  P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 13689

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    P1.04-109 - Antitumor Efficacy of Histone Deacetylase Inhibitor or in Combination with EGFR-TKI in Non-Small Cell Lung Cancer Cell Lines (ID 3090)

    09:30 - 09:30  |  Author(s): Y. Shi
    • Abstract
    • Slides

    Background:
    To investigate the antitumor efficacy of histone deacetylase inhibitor (HDACi) or in combination with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) cell lines.
    
    Methods:
    Ten NSCLC cell lines with varying mutation status were treated with chidamide (HDACi) and icotinib (TKI) alone or in combination. MTS assay was performed to determine IC~50~ of each drug or in combination. Cell cycle was analyzed by flow cytometry. Markers of epithelial-to-mesenchymal transition (E-cadherin), apoptosis (caspase-3, PARP) were determined by western blot.
    
    Results:
    The results demonstrated that A549 (TKI-resistant, KRAS-mutated), HCC827 (TKI-sensitive, EGFR-mutated), HCC827IR (TKI-resistant, EGFR-mutated) was sensitive to chidamide, the IC~50~ of these three cell lines was less than 0.5nM and the IC~50~ of the other seven cell lines was more than 5μM. Chidamide increased the sensitivity of icotinib synergistically in EGFR and KRAS wild type cells (H292, Calu-3), KRAS mutant cells (A549, H460), and TKI resistant EGFR mutant cells (H1650, H1650GR, HCC827IR, H1975), but the synergistic effect was most meaningful in H1975 (EGFR L858R and T790M mutation). We also found that H460 and Calu-3 had no E-cadherin expression, H1975 had low level of E-cadherin expression, and the other seven cell lines had relatively high levels of E-cadherin expression. Moreover, with the increasing dosage of chidamide, E-cadherin expression was significantly increased in H1975 cell line, but was not changed in chidamide sensitive cell lines. In addition, chidamide alone or in combination with icotinib could induce H1975 cell cycle arrest at G1/S phase, and reduce the expression of casepase-3 and PARP.
    
    Conclusion:
    These results suggest that chidamide as a single agent exhibits antiproliferative effectives in NSCLC cells with EGFR and KRAS mutations. The combination of chidamide and icotinib may be a beneficial treatment strategy for NSCLC with EGFR-T790M mutation. But the role of chidamide in the antiproliferative or synergistic mechanisms should be further explored
    
    

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