Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells
Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells
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DOI：
10.1016/j.jconrel.2007.08.016
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发表时间：
2007-12-04
影响因子：
10.8
通讯作者：
Kopecek, J.
中科院分区：
文献类型：
--
作者：
Malugin, A.;Kopeckova, P.;Kopecek, J.
尽管深入的研究，N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物结合阿霉素的细胞毒性的分子机制仍然不清楚。此外，释放的药物在细胞核中积累的能力也受到质疑。我们假设细胞周期进程的模式是一个有用的指标，游离阿霉素在细胞核中的存在及其与核DNA的相互作用。在本研究中，在培养的人卵巢癌A2780细胞中评价HPMA共聚物结合的阿霉素对细胞周期进程的影响。我们确定P-GFLG-DOX，而不是P-GG-DOX，以与游离DOX相同的方式启动细胞周期停滞和核碎裂，但具有时间延迟。我们的数据表明，药物从缀合物中释放是与缀合物相关的凋亡活性所需的。(c)2007 Elsevier B. V.保留所有权利。
Despite intensive study, the molecular mechanism for cell toxicity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound doxorubicin remains unclear. Moreover, the ability of the released drug to accumulate in the nucleus has also been questioned. We have hypothesized that the pattern of cell cycle progression is a useful indicator for the presence of free doxorubicin in the nucleus and its interaction with nuclear DNA. The effects of HPMA copolymer-bound doxorubicin on cell cycle progression were evaluated in this study in cultured human ovarian cancer A2780 cells. We determined that P-GFLG-DOX, but not P-GG-DOX, initiates cell cycle arrest and nuclear fragmentation in the same manner as free DOX, but with a time-delay. Our data indicate that drug release from the conjugate is required for the apoptotic activity associated with the conjugate. (c) 2007 Elsevier B.V. All rights reserved.