一种混合铂药物二氯乙酸铂（II）通过双细胞器靶向克服顺铂耐药性。
A hybrid platinum drug dichloroacetate-platinum(II) overcomes cisplatin drug resistance through dual organelle targeting.
作者信息
Zhang Yu, Guo Guannan, Ma Ben, Du Rong, Xiao Haihua, Yang Xiaoguang, Li Wenliang, Gao Ying, Li Yuxin, Jing Xiabin
机构信息
aNational Engineering Laboratory for Druggable Gene and Protein Screening bJilin Province Key Laboratory on Chemistry and Biology of Natural Drugs in Changbai Mountain, School of Life Sciences, Northeast Normal University cState Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences dSchool of Chemistry & Environmental Engineering, Changchun University of Science and Technology, Changchun, China.
出版信息
Anticancer Drugs. 2015 Aug;26(7):698-705. doi: 10.1097/CAD.0000000000000234.
A hybrid drug dichloroacetate-platinum(II) [DCA-Pt(II)] was found to overcome cisplatin drug resistance of ovarian cancer through a dual targeting mode, which is different from the mode of action of the present platinum (Pt) drugs used in clinics. DCA-Pt(II) exhibited remarkable cytotoxicity against both cisplatin-sensitive (A2780) and cisplatin-resistant (A2780DDP) ovarian cancer cells. The Pt and Pt-DNA adduct content test showed that there was less Pt cellular uptake and fewer Pt-DNA adducts were present after DCA-Pt(II) treatment compared with treatment with cisplatin, carboplatin, and some other drugs. In the study, the effects of DCA-Pt(II) on the cell cycle and apoptosis were also investigated, which showed that DCA-Pt(II) induced G2/M phase arrest and mitochondria-mediated apoptosis in both sensitive and resistant cells lines. Interestingly, DCA-Pt(II) had much greater effects on mitochondria in A2780DDP cell lines than in A2780 cell lines.
一种混合药物二氯乙酸盐 - 铂（II）[DCA - Pt（II）]被发现通过双重靶向模式克服卵巢癌的顺铂耐药性，这与目前临床使用的铂（Pt）类药物的作用模式不同。DCA - Pt（II）对顺铂敏感（A2780）和顺铂耐药（A2780DDP）的卵巢癌细胞均表现出显著的细胞毒性。铂和铂 - DNA加合物含量测试表明，与顺铂、卡铂和其他一些药物治疗相比，DCA - Pt（II）处理后细胞摄取的铂较少，且铂 - DNA加合物也较少。在该研究中，还研究了DCA - Pt（II）对细胞周期和凋亡的影响，结果表明DCA - Pt（II）在敏感和耐药细胞系中均诱导G2/M期阻滞和线粒体介导的凋亡。有趣的是，DCA - Pt（II）对A2780DDP细胞系中线粒体的影响比对A2780细胞系中的影响大得多。
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