| 崔晗 宦梦蕾 宋彦峰 刘道洲 叶威良 张邦乐 王玉琨 周四元.线粒体靶向TPP-DOX连接物的制备及其
逆转肿瘤耐药活性研究[J].,2015,15(9):1619-1622 |
| 线粒体靶向TPP-DOX连接物的制备及其
逆转肿瘤耐药活性研究 |
| Preparation of Mitochondrial Targeting TPP-DOX Conjugate to Overcomingthe Drug Resistance of Doxorubicin |
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| DOI： |
| 中文关键词: （3- 丙羧基）三苯基溴化膦 阿霉素 线粒体 多药耐药 |
| 英文关键词: (3-Carboxypropyl)Triphenylphosphonium Doxorubicin Mitochondria Multi-drug resistance |
| 基金项目:国家自然科学基金项目（81301303） |
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| 中文摘要: |
| 目的：阿霉素（DOX）是常用的抗肿瘤药物，但是它的毒副作用大，而且肿瘤细胞易对DOX 产生耐药，限制了其临床应用。本
研究利用肿瘤细胞线粒体跨膜电位较高的特性，将亲脂性阳离子（3-丙羧基）三苯基溴化膦（TPP）与DOX相连接制备具有线粒体
靶向功能的TPP-DOX，以期达到逆转肿瘤细胞耐药的目的。方法：以DOX、TPP为原料，合成TPP-DOX，通过核磁、质谱等方法进
行结构鉴定。采用MTT 方法研究TPP-DOX对KB 细胞、A549 细胞及耐DOX 肿瘤细胞MDA-MB-231/ADR的体外抗肿瘤活性。
采用激光共聚焦显微镜观察TPP-DOX 在肿瘤细胞内的分布。结果：TPP-DOX 对KB 细胞和A549 细胞的毒性低于DOX，
TPP-DOX 对耐DOX 肿瘤细胞MDA-MB-231/ADR 的毒性明显大于DOX。激光共聚焦显示TPP-DOX 分布于细胞核和线粒体
中。结论：TPP-DOX 具有线粒体靶向特性，可有效逆转肿瘤耐药，有进一步研究的价值。 |
| 英文摘要: |
| Objective:Doxorubicin (DOX) is a commonly used chemotherapy drug for tumor treatment. However, the severe side
effects and multiple drug resistance (MDR) hinder its clinical application. The mitochondrial trans-membrane potential is relative high,
thus lipophilic cations show high affinity with mitochondria. In this paper, (3-carboxyl) phenyl bromide phosphine (TPP) was conjugated
with DOX to prepare mitochondria targeting TPP-DOX to overcome drug resistance of tumor cells.Methods:TPP-DOX was synthesized
by connecting TPP and DOX. The structure of TPP-DOX was confirmed by 1HNMR and MS. The antitumor activity of TPP-DOX was
tested in vitro against KB cells, A549 cells and MDA-MB-231/ADR cells by MTT method. The laser confocal microscope was used to
observe the cellular uptake and distribution of the TPP-DOX in tumor cells.Results:TPP-DOX exhibited lower cytotoxicity than free
DOX on KB cells and A549 cells, but it showed higher cytotoxicity than free DOX on MDA-MB-231/ADR cells. Confocal microscopy
confirmed that TPP-DOX distributed in the mitochondria and nucleus.Conclusion:TPP-DOX can overcome drug resistance in tumor
cells, and it is worthy of further investigation. |
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