Cell-Penetrating Apoptotic Peptide/p53 DNA Nanocomplex as Adjuvant Therapy for Drug-Resistant Breast Cancer
文献类型：期刊论文
| 作者 | Wang, Huiyuan2 ; Wang, Huixin2; Liang, Jianming1,2; Jiang, Yifan2; Guo, Qianqian2; Peng, Huige2; Xu, Qin1; Huang, Yongzhuo2
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| 刊名 | MOLECULAR PHARMACEUTICS
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| 出版日期 | 2014-10 |
| 卷号 | 11期号:10页码:3352-3360 |
| 关键词 | cell-penetrating peptide drug resistance apoptosis apoptotic peptide p53 breast cancer AVPI |
| ISSN号 | 1543-8384 |
| DOI | 10.1021/mp5001058 |
| 文献子类 | Article |
| 英文摘要 | Drug resistance becomes a formidable challenge against effective cancer therapy. Defective apoptosis in cancer cells is a key factor responsible for chemoresistance or radioresistance. Promoting apoptosis is an important method to sensitize the resistant cells, thereby achieving successful treatment for MDR cancer. We present a strategy of codelivery of apoptotic AVPI peptide and p53 DNA as apoptosis-induction adjuvant therapy for combating the resistant breast cancer. AVPI tetrapeptide is poorly cell-permeable, thereby with very limited value for therapeutic use. Cell-penetrating chimeric AVPI derivative was developed by modification with an octa-arginine sequence (R-8). The AVPIR(8) is able to not only efficiently penetrate into tumor cells but also work as a vector for gene delivery by forming nanocomplexes based on its cationic R-8 moiety. The combination of AVPIR(8)/p53 DNA was selected for targeting apoptotic pathways, thereby sensitizing the cancer cells to chemotherapeutics. The anti-MDR effect was demonstrated both in vitro and in vivo. The synergistic use of AVPIR(8)/p53 significantly increased the sensitivity of the resistant tumor cells to the cytotoxic agent doxorubicin by inducing apoptosis, as demonstrated in the cellular studies. Importantly, the treatment improvement was also observed in the animal studies with resistant breast tumor model. Coadministration of AVPIR(8)/p53 enabled a full arrest of tumor growth combined with a reduced DOX dose, yielding a productive and safe cancer treatment. |
| WOS关键词 | CHEMOTHERAPY RESISTANCE ; P53 ; DELIVERY ; ACTIVATION ; STRATEGIES ; PATHWAY ; DESIGN ; DEATH |
| 资助项目 | National Basic Research Program of China (973 Program)[2013CB932503] ; National Basic Research Program of China (973 Program)[2014CB931900] ; NSFC, China[81172996] ; NSFC, China[81373357] ; Chinese Postdoctoral Science Foundation[2012M510097] ; Chinese Postdoctoral Science Foundation[2013T60478] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000342857000014 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276887]  |
| 专题 | 药物制剂研究中心 |
| 通讯作者 | Huang, Yongzhuo |
| 作者单位 | 1.Guangzhou Univ TCM, Trop Med Inst, Guangzhou 510450, Guangdong, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Huiyuan,Wang, Huixin,Liang, Jianming,et al. Cell-Penetrating Apoptotic Peptide/p53 DNA Nanocomplex as Adjuvant Therapy for Drug-Resistant Breast Cancer[J]. MOLECULAR PHARMACEUTICS,2014,11(10):3352-3360. |
| APA | Wang, Huiyuan.,Wang, Huixin.,Liang, Jianming.,Jiang, Yifan.,Guo, Qianqian.,...&Huang, Yongzhuo.(2014).Cell-Penetrating Apoptotic Peptide/p53 DNA Nanocomplex as Adjuvant Therapy for Drug-Resistant Breast Cancer.MOLECULAR PHARMACEUTICS,11(10),3352-3360. |
| MLA | Wang, Huiyuan,et al."Cell-Penetrating Apoptotic Peptide/p53 DNA Nanocomplex as Adjuvant Therapy for Drug-Resistant Breast Cancer".MOLECULAR PHARMACEUTICS 11.10(2014):3352-3360. |
入库方式： OAI收割
来源：上海药物研究所
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