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The HDAC inhibitor GCJ-490A suppresses c-Met expression through IKK? and overcomes gefitinib resistance in non-small cell lung cancer

文献类型：期刊论文

作者He, Ting1,2; Gao, Yinglei1; Fang, Yanfen1; Zhang, Yangming3; Zhang, Shuwei2,3; Nan, Fajun3; Ding, Jian1,2; Chen, Yi1,2
刊名CANCER BIOLOGY & MEDICINE
出版日期2022-08
卷号19期号:8页码:1172-1192
ISSN号2095-3941
关键词HDAC inhibitor c-Met IKK? NSCLC gefitinib
DOI10.20892/j.issn.2095-3941.2021.0130
文献子类Article
英文摘要inhibitory activity against HDAC1, HDAC3, and HDAC6. Because of the important roles of HDACs in lung cancer development and the high distribution of GCJ-490A in lung tissue, we explored the anti-tumor potency of GCJ-490A against non-small cell lung cancer (NSCLC) in vitro and in vivo in this study. Methods: The in vitro effects of GCJ-490A alone or combined with the EGFR inhibitor gefitinib against NSCLC were measured with proliferation, apoptosis, and colony formation assays. NSCLC xenograft models were used to investigate the efficacy of GCJ-490A combined with gefitinib for the treatment of NSCLC in vivo. Western blot assays, luciferase reporter assays, chromatin immunoprecipitation assays, quantitative real time-PCR, immunohistochemistry, and transcription factor activity assays were used to elucidate possible mechanisms. Results: GCJ-490A effectively inhibited NSCLC cell proliferation and induced apoptosis in vitro and in vivo. Interestingly, inhibition of HDAC1 and HDAC6 by GCJ-490A increased histone acetylation at the IKK?? promoter and enhanced IKK?? transcription, thus decreasing c-Met. Moreover, this c-Met downregulation was found to be essential for the synergistic anti-tumor activity of GCJ-490A and gefitinib. Conclusions: These findings highlight the promising potential of HDAC inhibitors in NSCLC treatment and provide a rational basis for the application of HDAC inhibitors in combination with EGFR inhibitors in clinical trials.
WOS关键词KAPPA-B ACTIVATION ; HISTONE DEACETYLASES ; PANOBINOSTAT ; COMBINATION ; THERAPY ; ALPHA ; POLYMORPHISM ; ERLOTINIB
WOS研究方向Oncology ; Research & Experimental Medicine
语种英语
出版者CHINA ANTI-CANCER ASSOC
WOS记录号WOS:000828829200001
源URL[http://119.78.100.183/handle/2S10ELR8/309359]  
专题新药研究国家重点实验室
通讯作者Nan, Fajun; Chen, Yi
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China;
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China;
3.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 He, Ting,Gao, Yinglei,Fang, Yanfen,et al. The HDAC inhibitor GCJ-490A suppresses c-Met expression through IKK? and overcomes gefitinib resistance in non-small cell lung cancer[J]. CANCER BIOLOGY & MEDICINE,2022,19(8):1172-1192.
APA He, Ting.,Gao, Yinglei.,Fang, Yanfen.,Zhang, Yangming.,Zhang, Shuwei.,...&Chen, Yi.(2022).The HDAC inhibitor GCJ-490A suppresses c-Met expression through IKK? and overcomes gefitinib resistance in non-small cell lung cancer.CANCER BIOLOGY & MEDICINE,19(8),1172-1192.
MLA He, Ting,et al."The HDAC inhibitor GCJ-490A suppresses c-Met expression through IKK? and overcomes gefitinib resistance in non-small cell lung cancer".CANCER BIOLOGY & MEDICINE 19.8(2022):1172-1192.

入库方式： OAI收割

来源：上海药物研究所

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