Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: Selective energy depletion.
Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: Selective energy depletion.
复制标题
DOI：
10.1054/bjoc.2001.2165
复制
发表时间：
2001-12-14
影响因子：
8.8
通讯作者：
Kabanov AV
中科院分区：
文献类型：
--
作者：
Batrakova EV;Li S;Elmquist WF;Miller DW;Alakhov VY;Kabanov AV
本文首次证明，暴露于聚（环氧乙烷）-聚（环氧丙烷）嵌段共聚物，普朗尼克P85的细胞，结果在MDR细胞中选择性ATP水平大幅下降。表达高水平功能性P-糖蛋白的细胞（MCF-7/ADR，KBv; LLC-MDR 1; Caco-2，牛脑微血管内皮细胞[BBMEC]）对Pluronic治疗高度响应，而低水平P-糖蛋白表达的细胞（MCF-7，KB，LLC-PK 1，人脐静脉内皮细胞[HUVEC] C2 C12成肌细胞）对此类治疗的响应性低得多。细胞毒性研究表明，普朗尼克作为一种化疗增敏剂，并加强多柔比星在MDR细胞中的细胞毒性作用。Pluronic抑制P-糖蛋白和致敏MDR细胞的能力似乎是ATP耗竭的结果。由于许多耐药机制是能量依赖性的，因此治疗MDR癌症的成功策略可以基于MDR细胞中的选择性能量消耗。因此，发现Pluronic P85的能量消耗效应及其增敏效应具有重要的理论和实际意义。© 2001年癌症研究运动http://www.bjcancer.com
This paper, for the first time, demonstrates that exposure of cells to the poly(ethylene oxide)-poly(propylene oxide) block copolymer, Pluronic P85, results in a substantial decrease in ATP levels selectively in MDR cells. Cells expressing high levels of functional P-glycoprotein (MCF-7/ADR, KBv; LLC-MDR1; Caco-2, bovine brain microvessel endothelial cells [BBMECs]) are highly responsive to Pluronic treatment, while cells with low levels of P-glycoprotein expression (MCF-7, KB, LLC-PK1, human umbilical vein endothelial cells [HUVECs] C2C12 myoblasts) are much less responsive to such treatment. Cytotoxicity studies suggest that Pluronic acts as a chemosensitizer and potentiates cytotoxic effects of doxorubicin in MDR cells. The ability of Pluronic to inhibit P-glycoprotein and sensitize MDR cells appears to be a result of ATP depletion. Because many mechanisms of drug resistance are energy dependent, a successful strategy for treating MDR cancer could be based on selective energy depletion in MDR cells. Therefore, the finding of the energy-depleting effects of Pluronic P85, in combination with its sensitization effects is of considerable theoretical and practical significance. © 2001 Cancer Research Campaign http://www.bjcancer.com
登录
查看更多内容
影响因子：
5.8
作者：
Alakhov, V;Klinski, E;Kabanov, A
通讯作者：
Kabanov, A
影响因子：
6.1
作者：
Fontaine, M;Elmquist, WF;Miller, DW
通讯作者：
Miller, DW
影响因子：
3.4
作者：
Rebbeor, JF;Senior, AE
通讯作者：
Senior, AE
影响因子：
3.7
作者：
Batrakova, EV;Han, HY;Kabanov, AV
通讯作者：
Kabanov, AV
人乳腺肿瘤细胞中的酸化不足及其对化学疗法的影响。
影响因子：
15.3
作者：
Altan, N;Chen, Y;Schindler, M;Simon, S M
通讯作者：
Simon, S M