Antitumor activity of histone deacetylase inhibitor chidamide alone or in combination with epidermal growth factor receptor tyrosine kinase inhibitor icotinib in NSCLC
Antitumor activity of histone deacetylase inhibitor chidamide alone or in combination with epidermal growth factor receptor tyrosine kinase inhibitor icotinib in NSCLC
复制标题
组蛋白脱乙酰酶抑制剂西达本胺单独或联合表皮生长因子受体酪氨酸激酶抑制剂埃克替尼治疗非小细胞肺癌的抗肿瘤活性
DOI：
10.7150/jca.28570
复制
发表时间：
2019-01
影响因子：
3.9
通讯作者：
Xiaohong Han
中科院分区：
文献类型：
--
作者：
Ningning Zhang;Caixia Liang;Wenya Song;Dan Tao;Jiarui Rao;Shuai Wang;Li Ma;Yuankai Shi;Xiaohong Han
本研究旨在研究组蛋白去乙酰化酶抑制剂（HDACi）西达米特单药或与表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）埃克替尼联合治疗非小细胞肺癌（NSCLC）的抗肿瘤疗效。在10个NSCLC细胞系中探索了单用或联合使用西达米特和埃克替尼的细胞活力、细胞周期、凋亡、蛋白表达和分子机制，并在裸鼠异种移植模型中进一步验证。西达胺显著降低A549、HCC 827、HCC 827 IR（埃克替尼耐药）细胞的存活率，协同增加埃克替尼对EGFR-TKI耐药细胞系的敏感性，尤其是H1975细胞。西达胺单独或与埃克替尼联合应用可通过抑制RAS/MAPK、PI 3 K/AKT和/或JAK/STAT通路的激活诱导细胞周期阻滞，并通过激活caspase 3和PARP诱导细胞凋亡。西达胺单用或与埃克替尼合用可抑制HCC 827、HCC 827 IR和H1975细胞中β-catenin的表达。西达米特通过恢复E-cadherin表达增加H1975细胞对埃克替尼的敏感性。此外，西达米特单独或与埃克替尼联合分别抑制无胸腺裸鼠中的HCC 827 IR和H1975异种移植物生长，且无明显副作用。西达胺或与埃克替尼联用对NSCLC细胞具有抗肿瘤活性，对NSCLC的治疗具有潜在的临床意义。
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.
登录
查看更多内容
影响因子：
--
作者：
Byeon HK;Na HJ;Yang YJ;Ko S;Yoon SO;Ku M;Yang J;Kim JW;Ban MJ;Kim JH;Kim DH;Kim JM;Choi EC;Kim CH;Yoon JH;Koh YW
通讯作者：
Koh YW
影响因子：
5.2
作者：
Gallagher SJ;Tiffen JC;Hersey P
通讯作者：
Hersey P
DOI：
10.4137/tog.s30534
发表时间：
2015
期刊：
Translational oncogenomics
影响因子：
--
作者：
Garajová I;Giovannetti E;Biasco G;Peters GJ
通讯作者：
Peters GJ
影响因子：
11.2
作者：
Eberlein CA;Stetson D;Markovets AA;Al-Kadhimi KJ;Lai Z;Fisher PR;Meador CB;Spitzler P;Ichihara E;Ross SJ;Ahdesmaki MJ;Ahmed A;Ratcliffe LE;O'Brien EL;Barnes CH;Brown H;Smith PD;Dry JR;Beran G;Thress KS;Dougherty B;Pao W;Cross DA
通讯作者：
Cross DA
DOI：
10.1016/j.apsb.2015.07.001
发表时间：
2015-09
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Huang L;Fu L
通讯作者：
Fu L