I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo

doi:10.1038/s41419-020-2515-z

科研成果详情

题名	I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo
作者	Liu, Zhengjun1; Li, Ping 2; Yang, Yong-qiang 3; Cai, Shang 3; Lin, Xiangwei 1; Chen, Min-bin 2; Guo, Hailei1
发表日期	2020-05-05
发表期刊	CELL DEATH & DISEASE 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	PANCREATIC-CANCER CELLS ; SPHINGOSINE KINASE-1 ; PROTEIN PHOSPHATASE ; TREATMENT OPTIONS ; TARGETED THERAPY ; INHIBITION ; RESISTANCE ; APOPTOSIS ; BRD4 ; RAS/RAF/MEK/ERK
摘要	Bromodomain-containing protein 4 (BRD4) is a potential therapeutic target of skin squamous cell carcinoma (SCC). I-BET726 is a novel BRD4 inhibitor. Its potential effect in skin SCC cells was tested in the present study. We show that I-BET726 potently inhibited survival, proliferation, cell cycle progression, and migration in established (A431/SCC-9/SCC-12/SCC-13 lines) and primary human skin SCC cells. I-BET726 induced significant apoptosis activation in skin SCC cells. It was more efficient in inhibiting skin SCC cells than known BRD4 inhibitors (JQ1, CPI203, and AZD5153). I-BET726 not only downregulated BRD4-regulated proteins (c-Myc, Bcl-2, and cyclin D1), but also inhibited sphingosine kinase 1 (SphK1) and Akt signalings in SCC cells. Restoring Akt activation, by a constitutively active S473D mutant Akt1 (caAkt1), partially inhibited I-BET726-induced cytotoxicity in A431 cells. In vivo, I-BET726 oral administration potently inhibited A431 xenograft growth in severe combined immunodeficient mice. Downregulation of BRD4-regulated proteins and inhibition of the SphK1-Akt signaling were detected in I-BET726-treated A431 xenograft tumor tissues. Together, I-BET726 inhibits skin SCC cell growth in vitro and in vivo.
资助项目	National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81773192, 81472786, 81902715, 81774109]; Foundation of Tumor Clinical and Basic Research Team of Affiliated Kunshan Hospital of Jiangsu University [KYC005]; Jiangsu Province Youth Medical Talents Project [QNRC2016527]; Jiangsu Province 333 Project Research Projects [2016-III-0367]; Kunshan Science and Technology Program [KS18057]; Jiangsu University Clinical Medical Science and Technology Development Fund [JLY20180012]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20171248, BK20180195]; Scientific Research Program for Young Talents of China National Nuclear Corporation (Shang Cai)
出版者	NATURE PUBLISHING GROUP
出版地	LONDON
ISSN	2041-4889
卷号	11 期号:5 页码:318
DOI	10.1038/s41419-020-2515-z
页数	12
WOS类目	Cell Biology
WOS研究方向	Cell Biology
WOS记录号	WOS:000532354400003
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	32371868
PMC记录号	PMC7200671
SCOPUSEID	2-s2.0-85084221543
通讯作者地址	[Guo, Hailei]Department of Burn and Plastic Surgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Immunology;Cellular and Molecular Neuroscience;Cell Biology;Cancer Research
TOP期刊	TOP期刊
引用统计	被引频次：7[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/7305
专题	第一临床医学院（信息与工程学院）、附属第一医院_外科学_整形外科附属第一医院
通讯作者	Guo, Hailei
作者单位	1.Department of Burn and Plastic Surgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 2.Department of Radiotherapy and Oncology,Affiliated Kunshan Hospital of Jiangsu University,Kunshan,China; 3.Department of Radiotherapy and Oncology,the Second Affiliated Hospital of Soochow University,Suzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Liu, Zhengjun,Li, Ping,Yang, Yong-qiang,et al. I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo[J]. CELL DEATH & DISEASE,2020,11(5):318.
APA	Liu, Zhengjun., Li, Ping., Yang, Yong-qiang., Cai, Shang., Lin, Xiangwei., ... & Guo, Hailei. (2020). I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo. CELL DEATH & DISEASE, 11(5), 318.
MLA	Liu, Zhengjun,et al."I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo".CELL DEATH & DISEASE 11.5(2020):318.