A 20(S)-protopanoxadiol derivative overcomes multi-drug resistance by antagonizing ATP-binding cassette subfamily B member 1 transporter function
文献类型：期刊论文
| 作者 | Chen, Gang1,4,5; Liu, Junhua2; Chen, Wantao1,4,5; Xu, Qin1,4,5; Xiao, Meng1,4,5; Hu, Lihong2; Mao, Li1,3; Wang, Xu1,4,5 |
| 刊名 | ONCOTARGET
 |
| 出版日期 | 2016-02-23 |
| 卷号 | 7期号:8页码:9389-9404 |
| ISSN号 | 1949-2553 |
| 关键词 | multi-drug resistance ABCB1 chemotherapy apoptosis panax ginseng |
| 文献子类 | Article |
| 英文摘要 | In cancer cells, failure of chemotherapy is often caused by the ATP-binding cassette subfamily B member 1 (ABCB1), and few drugs have been successfully developed to overcome ABCB1-mediated multi-drug resistance (MDR). To suppress ABCB1 activity, we previously designed and synthesized a new series of derivatives based on 20(S)-protopanoxadiol (PPD). In the present study, we investigated the role of PPD derivatives in the function of ABC transporters. Non-toxic concentrations of the PPD derivative PPD12 sensitized ABCB1-overexpressing cells to their anti-cancer substrates better than either the parental PPD or inactive PPD11. PPD12 increased intracellular accumulation of adriamycin and rhodamine123 in resistant cancer cells. Although PPD12 did not suppress the expression of ABCB1 mRNA or protein, it stimulated the activity of ABCB1 ATPase. Because PPD12 is a competitive inhibitor, it was predicted to bind to the large hydrophobic cavity of homology-modeled human ABCB1. PPD12 also enhanced the efficacy of adriamycin against ABCB1-overexpressing KB/VCR xenografts in nude mice. In conclusion, PPD12 enhances the efficacy of substrate drugs in ABCB1-overexpressing cancer cells. These findings suggest that a combination therapy consisting of PPD12 with conventional chemotherapeutic agents may be an effective treatment for ABCB1-mediated MDR cancer patients. |
| WOS关键词 | P-GLYCOPROTEIN ; CANCER-CELLS ; DRUG TRANSPORTERS ; IN-VITRO ; ABCB1 ; ABCG2 ; POLYMORPHISMS ; CHEMOTHERAPY ; PHARMACOLOGY ; MECHANISMS |
| 资助项目 | National Natural Science Foundation of China[81201715] ; National Natural Science Foundation of China[81572646] ; Shanghai Science and Technology Committee[14431905800] ; Chinese National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2013ZX09508104] |
| WOS研究方向 | Oncology ; Cell Biology |
| 语种 | 英语 |
| 出版者 | IMPACT JOURNALS LLC |
| WOS记录号 | WOS:000375618100070 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276137]  |
| 专题 | 上海中药现代化研究中心 |
| 通讯作者 | Hu, Lihong; Mao, Li; Wang, Xu |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Oral & Maxillofacial Head & Neck Oncol, Shanghai 200011, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Res Ctr Modernizat Tradit Chinese Med, Shanghai 201203, Peoples R China; 3.Univ Maryland, Sch Dent, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA 4.Shanghai Res Inst Stomatol, Shanghai 200011, Peoples R China; 5.Shanghai Key Lab Stomatol, Shanghai 200011, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Chen, Gang,Liu, Junhua,Chen, Wantao,et al. A 20(S)-protopanoxadiol derivative overcomes multi-drug resistance by antagonizing ATP-binding cassette subfamily B member 1 transporter function[J]. ONCOTARGET,2016,7(8):9389-9404. |
| APA | Chen, Gang.,Liu, Junhua.,Chen, Wantao.,Xu, Qin.,Xiao, Meng.,...&Wang, Xu.(2016).A 20(S)-protopanoxadiol derivative overcomes multi-drug resistance by antagonizing ATP-binding cassette subfamily B member 1 transporter function.ONCOTARGET,7(8),9389-9404. |
| MLA | Chen, Gang,et al."A 20(S)-protopanoxadiol derivative overcomes multi-drug resistance by antagonizing ATP-binding cassette subfamily B member 1 transporter function".ONCOTARGET 7.8(2016):9389-9404. |
入库方式： OAI收割
来源：上海药物研究所
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