H6, a novel hederagenin derivative, reverses multidrug resistance in vitro and in vivo
文献类型：期刊论文
| 作者 | Yang, Yanting2; Guan, Daokun2; Lei, Lei2,3; Lu, Jing2,4; Liu, Jia Qi2; Yang, Gangqiang2; Yan, Chunhong1,2; Zhai, Rong2; Tian, Jingwei2; Bi, Yi2 |
| 刊名 | TOXICOLOGY AND APPLIED PHARMACOLOGY
 |
| 出版日期 | 2018-02-15 |
| 卷号 | 341页码:98-105 |
| 关键词 | alpha-Hederagenin H6 Multidrug resistance P-glycoprotein Molecular docking |
| ISSN号 | 0041-008X |
| DOI | 10.1016/j.taap.2018.01.015 |
| 文献子类 | Article |
| 英文摘要 | Multidrug resistance (MDR) is a serious obstacle encountered in cancer treatment, in which the overexpression of P-glycoprotein (P-gp) plays an important role. Here, a novel alpha-hederagenin derivative, designated H6, was designed, synthesized and evaluated for its ability to reverse MDR. Our results showed that H6 could sensitize KBV and MCF7/T cells to paclitaxel and vincristine. Meanwhile, H6 could increase both rhodamine 123 and paclitaxel accumulation in MDR cells without affecting the expression of P-gp. Interestingly, siRNA knockdown of MDR1 further sensitized the cytotoxic activity of paclitaxel when co-administrated with H6. In addition, H6 could directly stimulate P-gp ATPase activity in vitro. Importantly, H6 enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors in nude mice. Finally, H6 showed high binding affinity with P-gp with a high docking score. Overall, we show H6 is a novel and potent MDR reversal agent, which has the potential to be administered in combination with conventional anticancer drugs. |
| WOS关键词 | CANCER DRUG-RESISTANCE ; P-GLYCOPROTEIN ; CELLS ; BREAST ; INHIBITORS ; TAXANE ; TRANSPORTER ; SENSITIVITY ; MECHANISMS ; STRATEGIES |
| 资助项目 | Taishan Scholar Project, National Natural Science Foundation of China[81441130] ; Taishan Scholar Project, National Natural Science Foundation of China[81728020] ; Key Research Project of Shandong Province[2017GSF18177] ; State Key Laboratory of Drug Research[SIMM1705KF-07] ; Graduate Innovation Foundation of Yantai University[YDZD1716] |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000425706900011 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279900]  |
| 专题 | 药物安全性评价中心 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 | Bi, Yi; Fu, Fenghua; Wang, Hongbo |
| 作者单位 | 1.Georgia Regents Univ, Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30602 USA 2.Yantai Univ, Collaborat Innovat Ctr Adv Drug Delivery Syst & B, Sch Pharm, Key Lab Mol Pharmacol & Drug Evaluat,Minist Educ, Yantai 264005, Peoples R China; 3.Chinese Acad Med Sci, Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Yang, Yanting,Guan, Daokun,Lei, Lei,et al. H6, a novel hederagenin derivative, reverses multidrug resistance in vitro and in vivo[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2018,341:98-105. |
| APA | Yang, Yanting.,Guan, Daokun.,Lei, Lei.,Lu, Jing.,Liu, Jia Qi.,...&Wang, Hongbo.(2018).H6, a novel hederagenin derivative, reverses multidrug resistance in vitro and in vivo.TOXICOLOGY AND APPLIED PHARMACOLOGY,341,98-105. |
| MLA | Yang, Yanting,et al."H6, a novel hederagenin derivative, reverses multidrug resistance in vitro and in vivo".TOXICOLOGY AND APPLIED PHARMACOLOGY 341(2018):98-105. |
入库方式： OAI收割
来源：上海药物研究所
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