Differential metabolic responses to pluronic in MDR and non-MDR cells: a novel pathway for chemosensitization of drug resistant cancers.
Differential metabolic responses to pluronic in MDR and non-MDR cells: a novel pathway for chemosensitization of drug resistant cancers.
复制标题
MDR和非MDR细胞中对pluron子的差异代谢反应：耐药性癌症化学敏化的新途径。
DOI：
10.1016/j.jconrel.2009.09.026
复制
发表时间：
2010-02-25
影响因子：
10.8
通讯作者：
Kabanov, Alexander V.
中科院分区：
文献类型：
--
作者：
Alakhova, Daria Yu.;Rapoport, Nataliya Y.;Batrakova, Elena V.;Timoshin, Alexander A.;Li, Shu;Nicholls, David;Alakhov, Valery Yu.;Kabanov, Alexander V.
Pluronic是一种合成的两亲性嵌段共聚物，是多药耐药（MDR）癌症的有效化疗增敏剂，在临床试验中显示出前景。它在MDR细胞中具有独特的活性，包括减少ATP池和抑制P-糖蛋白（Pgp），导致细胞中药物蓄积增加。这项工作表明，普朗尼克迅速（15分钟）易位到MDR细胞和共定位与线粒体。它抑制线粒体呼吸链的复合体I和复合体IV，减少耗氧量并导致MDR细胞中ATP耗竭。与非MDR对应物相比，这些效应对MDR细胞具有选择性和显著性，并在药物选择和Pgp转染的细胞模型中得到证实。此外，Pgp功能活性的抑制也消除了Pluronic对MDR细胞中细胞内ATP水平的影响，表明Pgp有助于MDR细胞线粒体中Pluronic分子“靶标”的反应性增加。Pluronic引起的MDR细胞线粒体呼吸损伤伴随着线粒体膜电位降低、ROS产生和细胞色素c释放。总之，这些作用最终增强了药物诱导的细胞凋亡，并有助于Pluronic对MDR肿瘤的有效化疗增敏。
A synthetic amphiphilic block copolymer, Pluronic, is a potent chemosensitizer of multidrug resistant (MDR) cancers that has shown promise in clinical trials. It has unique activities in MDR cells, which include a decrease in ATP pools and inhibition of P-glycoprotein (Pgp) resulting in increased drug accumulation in cells. This work demonstrates that Pluronic rapidly (15 min) translocates into MDR cells and co-localizes with the mitochondria. It inhibits complex I and complex IV of the mitochondria respiratory chain, decreases oxygen consumption and causes ATP depletion in MDR cells. These effects are selective and pronounced for MDR cells compared to non-MDR counterparts and demonstrated for both drug-selected and Pgp-transfected cell models. Furthermore, inhibition of Pgp functional activity also abolishes effects of Pluronic on intracellular ATP levels in MDR cells suggesting that Pgp contributes to increased responsiveness of molecular “targets” of Pluronic in the mitochondria of MDR cells. The Pluronic-caused impairment of respiration in mitochondria of MDR cells is accompanied with a decrease in mitochondria membrane potential, production of ROS, and release of cytochrome c. Altogether these effects eventually enhance drug-induced apoptosis and contribute to potent chemosensitization of MDR tumors by Pluronic.
登录
查看更多内容
影响因子：
4.7
作者：
Miller, DW;Batrakova, EV;Kabanov, AV
通讯作者：
Kabanov, AV
DOI：
10.1006/bmmb.1994.1004
发表时间：
1994-02-01
期刊：
BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY
影响因子：
--
作者：
BIRCHMACHIN, MA;BRIGGS, HL;TURNBULL, DM
通讯作者：
TURNBULL, DM
影响因子：
3.9
作者：
BRIERLEY, GP;SCOTT, KM;MEROLA, AJ
通讯作者：
MEROLA, AJ
I阶段剂量升级和药代动力学研究对晚期癌症患者的pluronic聚合物结合的阿霉素（SP1049C）。
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
8.8
作者：
Batrakova EV;Li S;Elmquist WF;Miller DW;Alakhov VY;Kabanov AV
通讯作者：
Kabanov AV