Prodrug-Like, PEGylated Protein Toxin Trichosanthin for Reversal of Chemoresistance
文献类型：期刊论文
| 作者 | Chen, Yingzhi1,2; Zhang, Meng1,2; Jin, Hongyue1,2; Tang, Yisi3; Wu, Aihua3; Huang, Yongzhuo2
|
| 刊名 | MOLECULAR PHARMACEUTICS
 |
| 出版日期 | 2017-05 |
| 卷号 | 14期号:5页码:1429-1438 |
| 关键词 | multidrug resistance trichosanthin matrix metalloproteinase paclitaxel caspase 9 phosphorylation intein-mediated protein ligation PEGylation |
| ISSN号 | 1543-8384 |
| DOI | 10.1021/acs.molpharmaceut.6b00987 |
| 文献子类 | Article |
| 英文摘要 | Multidrug resistance (MDR) is a main obstacle in cancer chemotherapy. The MDR mechanisms involve P-glycoprotein (P-gp) overexpression, abnormality of,apoptoiis-related protein, and altered expression of drug-targeting proteihs. Therapeutic proteins ate emerging as candidates for Overcoming cancer MDR because of not only their large molecular size that potentially circumvents the P-gp-mediated drug efflux but also their distinctive bioactivity distinguished from small-molecular drugs. Herein we report trichosanthin, a plant protein toxin, possesses synergistic effect with paditaxeI (PTX) in the PTX-resistance A549/T nonsmall cell lung cancer (NSCLC) cells, by reversing PTX-caused caspase 9 phosphorylation and inducing caspase 3-dependent apopiosis. Moreover, via intein-mediated site-specific protein ligation; a matrix metalloproteinase (MMP)-activatable cell-penetrating trichosanthin delivery system was constructed by modification of a cell-penetrating peptide and MMP-2-sensitive PEGylation to overcome the limitation of in vivo application of trichosanthin, by improving the short half-life and poor tumor targeting, as well as immunogenicity. In a mouse model bearing A549/T tumor, the MMP-activatable trichosanthin was further tested for its application for MDR reversal in combination with PTX liposomes. The delivery system showed synergy effect with PTX-loaded liposome in treating MDR cancer in vivo. |
| WOS关键词 | RIBOSOME-INACTIVATING PROTEINS ; RESISTANT BREAST-CANCER ; APOPTOSIS ; CASPASE-9 ; DELIVERY ; CELLS ; PHOSPHORYLATION ; MECHANISMS ; THERAPY ; DILEMMA |
| 资助项目 | 973 Program, China[2014CB931900] ; 973 Program, China[2013CB932503] ; NSFC, China[81172996] ; NSFC, China[81422048] ; NSFC, China[81521005] ; NSFC, China[81673382] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000400633300011 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272687]  |
| 专题 | 药物制剂研究中心 |
| 通讯作者 | Huang, Yongzhuo |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Hai Ke Rd, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 3.Guangzhou Univ Chinese Med, Trop Med Inst, 12 Ji Chang Rd, Guangzhou 510450, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Yingzhi,Zhang, Meng,Jin, Hongyue,et al. Prodrug-Like, PEGylated Protein Toxin Trichosanthin for Reversal of Chemoresistance[J]. MOLECULAR PHARMACEUTICS,2017,14(5):1429-1438. |
| APA | Chen, Yingzhi,Zhang, Meng,Jin, Hongyue,Tang, Yisi,Wu, Aihua,&Huang, Yongzhuo.(2017).Prodrug-Like, PEGylated Protein Toxin Trichosanthin for Reversal of Chemoresistance.MOLECULAR PHARMACEUTICS,14(5),1429-1438. |
| MLA | Chen, Yingzhi,et al."Prodrug-Like, PEGylated Protein Toxin Trichosanthin for Reversal of Chemoresistance".MOLECULAR PHARMACEUTICS 14.5(2017):1429-1438. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。