Stimulation of tumor growth in vitro and in vivo by suramin on the VX2 model.
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 tested in vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suramin in vivo and in 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 micrograms/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluated in vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis and in 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 micrograms/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.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D009368:Neoplasm Transplantation; D011817:Rabbits; D013268:Stimulation, Chemical; D013498:Suramin / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006133:Growth Substances; D014344:Trypanocidal Agents; D013498:Suramin