Antitumor activity of histone deacetylase inhibitor chidamide alone or in combination with epidermal growth factor receptor tyrosine kinase inhibitor icotinib in NSCLC

Zhang, Ningning; Liang, Caixia; Song, Wenya; Tao, Dan; Yao, Jiarui; Wang, Shuai; Ma, Li; Shi, Yuankai; Han, Xiaohong

doi:10.7150/jca.28570

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J Cancer 2019; 10(5):1275-1287. doi:10.7150/jca.28570 This issue Cite

Research Paper

Antitumor activity of histone deacetylase inhibitor chidamide alone or in combination with epidermal growth factor receptor tyrosine kinase inhibitor icotinib in NSCLC

Ningning Zhang¹, Caixia Liang¹, Wenya Song¹, Dan Tao¹, Jiarui Yao¹, Shuai Wang¹, Li Ma¹, Yuankai Shi^1✉, Xiaohong Han^1,2✉

1. Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China.
2. Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China.

Citation:

Zhang N, Liang C, Song W, Tao D, Yao J, Wang S, Ma L, Shi Y, Han X. Antitumor activity of histone deacetylase inhibitor chidamide alone or in combination with epidermal growth factor receptor tyrosine kinase inhibitor icotinib in NSCLC. J Cancer 2019; 10(5):1275-1287. doi:10.7150/jca.28570. https://www.jcancer.org/v10p1275.htm

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Abstract

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 β-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.

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APA

Zhang, N., Liang, C., Song, W., Tao, D., Yao, J., Wang, S., Ma, L., Shi, Y., Han, X. (2019). Antitumor activity of histone deacetylase inhibitor chidamide alone or in combination with epidermal growth factor receptor tyrosine kinase inhibitor icotinib in NSCLC. Journal of Cancer, 10(5), 1275-1287. https://doi.org/10.7150/jca.28570.

ACS

Zhang, N.; Liang, C.; Song, W.; Tao, D.; Yao, J.; Wang, S.; Ma, L.; Shi, Y.; Han, X. Antitumor activity of histone deacetylase inhibitor chidamide alone or in combination with epidermal growth factor receptor tyrosine kinase inhibitor icotinib in NSCLC. J. Cancer 2019, 10 (5), 1275-1287. DOI: 10.7150/jca.28570.

NLM

CSE

Zhang N, Liang C, Song W, Tao D, Yao J, Wang S, Ma L, Shi Y, Han X. 2019. Antitumor activity of histone deacetylase inhibitor chidamide alone or in combination with epidermal growth factor receptor tyrosine kinase inhibitor icotinib in NSCLC. J Cancer. 10(5):1275-1287.

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