6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib

doi:10.1096/fj.201700306RR

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib
	Liu, Yanning 7; Lou, Guohua 7; Norton, John T.1; Wang, Chen 1; Kandela, Irawati 3; Tang, Shuai 4; Shank, Nathaniel I.5; Gupta, Pankaj 5; Huang, Min4 ; Avram, Michael J.6
刊名	FASEB JOURNAL
	2017-12
卷号	31 期号:12 页码:5453-5465
关键词	MEAN HCC therapeutic combination treatment C-MYC inhibition
ISSN号	0892-6638
DOI	10.1096/fj.201700306RR
文献子类	Article
英文摘要	Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC. Treatment by MEAN at an effective dose for 6 wk was well toleratedby animals. Combined therapy using both sorafenib and MEAN enhanced tumor growth inhibition over monotherapy with either agent. Additional experiments revealed that MEAN inhibited tumor growth through mechanisms distinct from those of either its parent compound, amonafide, or sorafenib. MEAN suppressed C-MYC expression and increased expression of several tumor suppressor genes, including Src homology region 2 domain-containing phosphatase-1 (SHP-1) andTXNIP (thioredoxin-interacting protein). As an encouraging feature for envisioned clinical application, the IC50 of MEAN was not significantly changed in several drug-resistant cell lines with activated P-glycoprotein drug efflux pumps compared to drug-sensitive parent cells, demonstrating the ability of MEAN to be effective in cells resistant to existing chemotherapy regimens. MEAN is a promising candidate for clinical development as a single-agent therapy or in combination with sorafenib for the management of HCC.
资助项目	International Science and Technology Cooperation Project (Re-Innovation Industrialization)[2012C14028] ; H. Foundation[00000000] ; Rosenberg Foundation of the Robert H. Lurie Comprehensive Cancer Center[00000000] ; U.S. National Institutes of Health (NIH) National Institute of General Medical Sciences[2 R01 GM078555-05] ; NIH[00000000]
WOS关键词	TYROSINE-PHOSPHATASE SHP-1 ; LIVER-TRANSPLANTATION ; MOLECULAR-MECHANISMS ; GLUCOSE-HOMEOSTASIS ; ANTICANCER AGENTS ; CANCER ; TXNIP ; AMONAFIDE ; CELLS ; SIRT1
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
语种	英语
出版者	FEDERATION AMER SOC EXP BIOL
WOS记录号	WOS:000416588300028
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272376]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Chen, Zhi; Huang, Sui
作者单位	1.Northwestern Univ, Dept Cell & Mol Biol, Feinberg Sch Med, 303 E Chicago Ave, Chicago, IL 60614 USA; 2.Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60614 USA; 3.Northwestern Univ, Dev Therapeut Core, Chicago, IL 60614 USA; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai, Peoples R China; 5.NIDDK, NIH, Bethesda, MD USA 6.Northwestern Univ, Dept Anesthesiol, Feinberg Sch Med, Chicago, IL 60614 USA; 7.Zhejiang Univ, Affiliated Hosp 1, Collaborat Innovat Ctr Diag & Treatment Infect Di, State Key Lab Infect Dis Diag & Treatment,Coll Me, Hangzhou, Zhejiang, Peoples R China;
推荐引用方式 GB/T 7714	Liu, Yanning,Lou, Guohua,Norton, John T.,et al. 6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib[J]. FASEB JOURNAL,2017,31(12):5453-5465.
APA	Liu, Yanning.,Lou, Guohua.,Norton, John T..,Wang, Chen.,Kandela, Irawati.,...&Huang, Sui.(2017).6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib.FASEB JOURNAL,31(12),5453-5465.
MLA	Liu, Yanning,et al."6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib".FASEB JOURNAL 31.12(2017):5453-5465.