Exploration on Anti-Multidrug-Resistant Molecular Mechanisms of Salvicine and Characterization of Salvicine-Resistant A549/SAL Cell Line
文献类型：期刊论文
| 作者 | Liao Zehong; Ding Jian
|
| 刊名 | Journal of the Graduate School of the Academy of Sciences
 |
| 出版日期 | 2004 |
| 卷号 | 21期号:4页码:549-556 |
| 关键词 | salvicine multidrug resistance mdr-1 c-jun A549/SAL cells |
| ISSN号 | 1002-1175 |
| 其他题名 | 沙尔威辛抗肿瘤多药耐药分子机制及耐药特性研究 |
| 文献子类 | Article |
| 英文摘要 | Multidrug resistance (MDR) is a major clinical problem in treating human cancers with conventional chemotherapeutic drugs. This study demonstrated that salvicine, a novel antitumor compound under clinical trial, exerted direct cytotoxicity against MDR tumor cells and down-regulated mdr-1/P-glycoprotein (P-gp) expression simultaneously. Salvicine effectively killed MDR sublines, such as K562/A02, KB/VCR and MCF-7/ADR, and parental K562, KB, and MCF-7 cell lines to an equivalent degree. Its cytotoxic activities were much more potent than those of several classical anticancer drugs. Salvicine induced the downregulation of mdr-1 gene and P-gp expression,while not affecting MRP and LRP expression. Anti-MDR mechanism exploration revealed that transcription factor c-Jun played a principal role in downregulation of mdr-1 expression and induction of apoptosis by salvicine. Levels of c-jun expression were enhanced by salvicine prior to reduction of mdr-1 expression in K562/A02 cells. Moreover, c-jun antisense oligodeoxynucleotides (AODs)prevented salvicine-stimulated enhancement of c-Jun protein and reduction of mdr-1 gene expression, but did not affect the increase in c-jun mRNA levels. Salvicine promoted phosphorylation of JNK kinase and c-Jun protein and enhanced DNA binding activity of transcription factor AP1. Additionally, c-jun AODs also inhibited salvicine-induced apoptosis and cytotoxicity. Finally, salvicine was further shown not to induce a tumor MDR phenotype. We established a salvicine-resistant tumor cell subline, A549/SAL, which displayed 8.91-fold resistance to salvicine and an average of 6. 70-fold resistance to the antimetabolites. The subline, however, was not resistant to alkylating agents,platinum compounds, and other naturally-derived antineoplastics. |
| 资助项目 | 中科院创新工程基金[00000000] ; National Natural Science Foundation of China[00000000] ; 国家863计划[00000000] |
| WOS研究方向 | Oncology (provided by Clarivate Analytics) |
| 语种 | 英语 |
| CSCD记录号 | CSCD:1857925 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/268370]  |
| 专题 | 药理学第一研究室 |
| 作者单位 | Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of' Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China. |
| 推荐引用方式 GB/T 7714 | Liao Zehong,Ding Jian. Exploration on Anti-Multidrug-Resistant Molecular Mechanisms of Salvicine and Characterization of Salvicine-Resistant A549/SAL Cell Line[J]. Journal of the Graduate School of the Academy of Sciences,2004,21(4):549-556. |
| APA | Liao Zehong,&Ding Jian.(2004).Exploration on Anti-Multidrug-Resistant Molecular Mechanisms of Salvicine and Characterization of Salvicine-Resistant A549/SAL Cell Line.Journal of the Graduate School of the Academy of Sciences,21(4),549-556. |
| MLA | Liao Zehong,et al."Exploration on Anti-Multidrug-Resistant Molecular Mechanisms of Salvicine and Characterization of Salvicine-Resistant A549/SAL Cell Line".Journal of the Graduate School of the Academy of Sciences 21.4(2004):549-556. |
入库方式： OAI收割
来源：上海药物研究所
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