6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib
文献类型：期刊论文
| 作者 | Liu, Yanning7; Lou, Guohua7; Norton, John T.1; Wang, Chen1; Kandela, Irawati3; Tang, Shuai4; Shank, Nathaniel I.5; Gupta, Pankaj5; Huang, Min4 ; Avram, Michael J.6
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| 刊名 | FASEB JOURNAL
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| 出版日期 | 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. |
| WOS关键词 | TYROSINE-PHOSPHATASE SHP-1 ; LIVER-TRANSPLANTATION ; MOLECULAR-MECHANISMS ; GLUCOSE-HOMEOSTASIS ; ANTICANCER AGENTS ; CANCER ; TXNIP ; AMONAFIDE ; CELLS ; SIRT1 |
| 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研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000416588300028 |
| 出版者 | FEDERATION AMER SOC EXP BIOL |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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