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Stimulation of tumor growthin vitro andin vivo by suramin on the VX2 model
Authors:Luis H. Ramirez  Morbize Juliéron  Marc Bonnay  Serge Koscielny  Zhongxin Zhao  Alain Gouyette  Jean-Nicolas Munck
Affiliation:(1) Département de Médecine, Institut Gustave-Roussy, 39, rue Camille Desmoulins, 94800 Villejuif, France;(2) Département de Chirurgie Cervicofaciale, Institut Gustave-Roussy, 39, rue Camille Desmoulins, 94800 Villejuif, France;(3) Laboratoire de Biologie Clinique, Institut Gustave-Roussy, 39, rue Camille Desmoulins, 94800 Villejuif, France;(4) Laboratoire de Pharmacologie Clinique URA 147 CNRS, Institut Gustave-Roussy, 39, rue Camille Desmoulins, 94800 Villejuif, France
Abstract:Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs. Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits, and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further trials in patients with squamous cell carcinomas.
Keywords:suramin  VX2 tumor  pharmacokinetics  tumor promotion
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