线粒体靶向DQA-DOX连接物的制备及其逆转肿瘤耐药活性研究  

Preparation and anti-tumor activity of mitochondrial targeting DQA-DOX conjugate

作　　者：宋彦峰[1] 滕增辉[1] 崔晗[1] 刘道洲[1] 叶威良[1] 张邦乐[1] 周四元[1] 

机构地区：[1]第四军医大学药学院药剂学教研室,西安710032

出　　处：《西北药学杂志》2015年第3期283-286,共4页Northwest Pharmaceutical Journal

基　　金：陕西省自然科学基金(编号:2013JQ4026)

摘　　要：目的为寻找线粒体靶向的抗肿瘤药物,将阿霉素(doxorubicin,DOX)与地喹氯铵(dequalinium,DQA)连接形成DQADOX,观察DQA-DOX的抗肿瘤作用。方法合成DQA-DOX连接物,通过MTT、细胞摄取实验对DQA-DOX进行体外抗肿瘤活性研究。结果细胞毒性实验显示:与游离DOX相比,DQA-DOX对A549细胞的毒性比游离DOX明显低,但DQA-DOX对耐DOX细胞MCF-7/ADR细胞的毒性比游离DOX显著增强。共聚焦显微镜观察结果显示:MCF-7/ADR细胞给予游离DOX后,DOX在细胞浆和细胞核分布得很少;MCF-7/ADR细胞给予DQA-DOX后,DQA-DOX特异性地分布于线粒体。结论DQA-DOX具有对抗阿霉素耐药作用,有进一步研究的价值。Objective In order to find mitochondrial targeting anti‐tumor molecule ,DQA‐DOX conjugate was synthesized and its an‐titumor activity was evaluated .Methods The anti‐tumor activity of DQA‐DOX invitro was studied by MTT method .Subcellular distribution of DQA‐DOX in MCF‐7/ADR cells was observed with confocal laser scanning microscopy . Result DQA‐DOX showed lower cytotoxicity as compared with free DOX on A 549 cells .However ,on MCF‐7/ADR cells ,DQA‐DOX exhibited higher cytotoxicity as compared with free DOX .DQA‐DOX mainly distributed in MCF‐7/ADR cells of mitochondria .Conclusion DQA‐DOX can overcome the resistant of DOX on MCF‐7/ADR cells .DQA‐DOX is worthy of further investigation .

关 键 词：地喹氯铵 阿霉素 线粒体 多药耐药 

分 类 号：R944[医药卫生—药剂学]