Journal
JOURNAL OF CANCER
Volume 10, Issue 5, Pages 1275-1287Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.28570
Keywords
-
Categories
Funding
- National High Technology Research and Development Program of China (863 Program) [2011AA02A110]
- Chinese National Major Project for New Drug Innovation [2017ZX09304015]
- Beijing Municipal Science and Technology Commission Major Project [D141100000214003, D141100000214005]
- Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs-2012 Ladder Program [Z121102009212055]
- National Natural Science Foundation of China [81871739, 81472752]
- Specialized Research Fund for the Doctoral Program of Higher Education [20131106130004]
- Peking Union Medical College Graduate Students Innovation Found [2012-1002-054]
Ask authors/readers for more resources
The study was performed to investigate the antitumor efficacy of histone deacetylase inhibitor (HDACi) chidamide alone or with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) icotinib in non-small cell lung cancer (NSCLC). The cell viability, cell cycle, apoptosis, protein expression, and the molecular mechanisms were explored among ten NSCLC cell lines with chidamide and icotinib alone or in combination, and further validated in xenograft models of nude mice. Chidamide significantly reduced the viability of A549, HCC827, HCC827IR (icotinib resistant) cells, increased the sensitivity of icotinib synergistically in EGFR-TKI resistant cell line, especially in H1975 cells. Chidamide alone or combined with icotinib induced cell cycle arrest by inhibiting the activation of RAS/MAPK, PI3K/AKT and/or JAK/STAT pathways, and caused apoptosis by activating caspase 3 and PARP. Chidamide alone or with icotinib suppressed beta-catenin expression in HCC827, HCC827IR, and H1975 cells. The sensitivity of H1975 cells to icotinib was increased by chidamide through restoring E-cadherin expression. Furthermore, chidamide alone or in combination with icotinib inhibited HCC827IR and H1975 xenograft growth in athymic nude mice, respectively, with no appreciable side effects. Chidamide or combinating with icotinib exhibits antitumor activity in NSCLC cells, and has potential clinical implication for the treatment of NSCLC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available