The therapeutic potential of a novel non-ATP-competitive fibroblast growth factor receptor 1 inhibitor on gastric cancer

doi:10.1097/CAD.0000000000000195

科研成果详情

题名	The therapeutic potential of a novel non-ATP-competitive fibroblast growth factor receptor 1 inhibitor on gastric cancer
作者	Xu, Chaochao 1,3; Li, Wulan1,2; Qiu, Peihong 1; Xia, Yiqun 3; Du, Xiaojing3; Wang, Fen 5; Shen, Lailai 1; Chen, Qiuxiang 3; Zhao, Yunjie1; Jin, Rong 3,4; Wu, Jianzhang1; Liang, Guang1; Li, Xiaokun1
发表日期	2015-04
发表期刊	ANTI-CANCER DRUGS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	fibroblast growth factor receptor 1 gastric cancer molecular targeted therapy
其他关键词	NORDIHYDROGUAIARETIC ACID NDGA ; SELECTIVE INHIBITOR ; GENE AMPLIFICATION ; ANTITUMOR-ACTIVITY ; FGFR2 INHIBITOR ; DISCOVERY ; KINASES ; FAMILY ; BLOCKS ; IGF-1
摘要	Previous studies showed that fibroblast growth factor receptor 1 (FGFR1) is an attractive target in gastric cancer therapy. In the current study, we aimed to investigate whether the compound L6123, a novel non-ATP-competitive FGFR1 inhibitor, could show better antitumor activity than the leading compound, nordihydroguaiaretic acid (NDGA), in FGFR1-overexpressing gastric cancer cells. Using an MTT assay, we investigated the inhibitory effect of L6123 on the viability of three gastric cancer cells (MGC-803, SGC-7901, and BGC-823) overexpressing FGFR1, wild-type mouse embryonic fibroblast (MEF-WT), and MEF expressing FGFR1, FGFR2, and FRS2 gene knockout (MEF-FGFR1-FGFR2-FRS2-ko). We studied the antitumor mechanism of L6123 against the gastric cancer cell line SGC-7901 by western blot analysis. The antitumor effects of L6123 on the gastric cancer cell line SGC-7901 were detected by flow cytometry, Hoechst staining, western blot analysis, and Transwell invasion assay. L6123 had lower IC50 in all three gastric cancer cells than NDGA and showed better inhibitory activity against MEF-WT cells than against MEF-FGFR1-FGFR2-FRS2-ko cells. In the SGC-7901 gastric cell, L6123 inhibited the FGF2-induced phosphorylation of FGFR1/FRS2/ERK1/2 in a dose-dependent manner, induced the activation of the apoptosis-related proteins, cleaved-PARP and cleaved-caspase-3, decreased the expression of pro-caspase-3 and Bcl-2, and induced tumor cell apoptosis. L6123 also dose-dependently reduced cell invasion ability, and showed better activity than NDGA at the same concentration. A novel non-ATP-competitive inhibitor L6123 showed excellent antigastric cancer activity by inhibiting the FGFR1 signaling pathway. Thus, we discovered a potential agent for the treatment of FGFR1-overexpressing gastric cancer.
资助项目	ZheJiang Province Natural Science Funding of China [LY12H30004, LY14H160044]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81102310, 81402839, 81272462]; Technology Foundation for Medical Science of Zhejiang Province [2012KYA129, 2012 KYB127]
出版者	LIPPINCOTT WILLIAMS & WILKINS
出版地	PHILADELPHIA
ISSN	0959-4973
EISSN	1473-5741
卷号	26 期号:4 页码:379-387
DOI	10.1097/CAD.0000000000000195
页数	9
WOS类目	Oncology ; Pharmacology & Pharmacy
WOS研究方向	Oncology ; Pharmacology & Pharmacy
WOS记录号	WOS:000351266700002
收录类别	SCIE ; SCOPUS
URL	查看原文
PubMed ID	25521558
SCOPUSEID	2-s2.0-84925463295
通讯作者地址	[Jin, Rong]Department of Digestive Diseases, Wenzhou Medical University,Wenzhou,323000,China
Scopus学科分类	Medicine (all)
引用统计	被引频次：8[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/4299
专题	药学院（分析测试中心）_生物有机与药物化学研究中心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_计算机与信息管理系第一临床医学院（信息与工程学院）、附属第一医院_流行病学第一临床医学院（信息与工程学院）、附属第一医院_内科学_消化内科
通讯作者	Jin, Rong
作者单位	1.Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University,Wenzhou,325035,China; 2.College of Information Science and Computer Engineering, Wenzhou Medical University,Wenzhou,China; 3.Department of Digestive Diseases, Wenzhou Medical University,Wenzhou,323000,China; 4.Department of Epidemiology, Wenzhou Medical University,Wenzhou,China; 5.Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M University,Houston,United States
第一作者单位	生物有机与药物化学研究中心; 温州医科大学
通讯作者单位	温州医科大学
第一作者的第一单位	生物有机与药物化学研究中心
推荐引用方式 GB/T 7714	Xu, Chaochao,Li, Wulan,Qiu, Peihong,et al. The therapeutic potential of a novel non-ATP-competitive fibroblast growth factor receptor 1 inhibitor on gastric cancer[J]. ANTI-CANCER DRUGS,2015,26(4):379-387.
APA	Xu, Chaochao., Li, Wulan., Qiu, Peihong., Xia, Yiqun., Du, Xiaojing., ... & Li, Xiaokun. (2015). The therapeutic potential of a novel non-ATP-competitive fibroblast growth factor receptor 1 inhibitor on gastric cancer. ANTI-CANCER DRUGS, 26(4), 379-387.
MLA	Xu, Chaochao,et al."The therapeutic potential of a novel non-ATP-competitive fibroblast growth factor receptor 1 inhibitor on gastric cancer".ANTI-CANCER DRUGS 26.4(2015):379-387.