The influence of temperature on antiproliferative effects, cellular uptake and DNA platination of the clinically employed Pt(II)-drugs

被引：50

作者：

Gabano, Elisabetta ^{[1
]}

Colangelo, Donato ^{[2
]}

Ghezzi, Anna Rita ^{[2
]}

Osella, Domenico ^{[1
]}

机构：

[1] Univ Piemonte Orientale, Dipartimento Sci Ambientali & Vita, I-15100 Alessandria, Italy

[2] Univ Piemonte Orientale, Dipartimento Sci Med, I-28100 Novara, Italy

来源：

JOURNAL OF INORGANIC BIOCHEMISTRY | 2008年 / 102卷 / 04期

关键词：

cisplatin-like complexes; hyperthermia; platinum uptake; ICP-MS;

D O I：

10.1016/j.jinorgbio.2007.10.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cellular uptake of a drug is one of the most important factors influencing its pharmacodynamics and pharmacokinetics. Our laboratory has previously studied platinum uptake following cisplatin, carboplatin and oxaliplatin treatment at sub-lethal doses of selected tumour cell lines. Here we report on the influence of temperature on dose-dependent antiproliferative effects, cellular uptake and DNA platination of these platinum-based drugs tested on MCF-7 human mammary carcinoma cell line. Inductively coupled plasma-mass spectrometry (ICP-MS) technique has been chosen to perform Pt determinations on cells treated with drug concentrations similar with those usually found in vivo in human plasma. The high sensitivity and analytical rapidity of this technique made possible to carry out a very large amount of Pt determinations (about 300) necessary for this study. Hypertherima (43 degrees C) proved a synergistic effect with cisplatin on cell growth inhibition, while only an additive effect was demonstrated for carboplatin and oxaliplatin. This behaviour might be explained by the higher DNA platination ratio between data at 43 and 37 degrees C of cisplatin with respect to those of carboplatin and oxaliplatin. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：629 / 635

页数：7

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