Efficacy of suramin against human prostate carcinoma DU145 xenografts in nude mice

Purpose: Toward developing a model to study the mechanism of action of suramin against prostate cancer, we identified the effect of suramin on the growth of xenografts of the androgen-independent human prostate carcinoma DU145 cell line and our subline of suramin-resistant (SR) DU145 cells which are less responsive to suramin in vitro, Methods: Athymic nude mice bearing DU145 or SR DU145 xenografts were treated intraperitoneally (IP) once weekly with normal saline (vehicle control) or suramin in normal saline. For data analysis mice were grouped as follows: 0 mg/kg (controls), <210 mg/kg, 210 to 260 mg/kg, or >260 mg/kg suramin. Results: The growth of DU145 xenografts was slowed by treatment with 210 to 260 mg/kg suramin IP once weekly: differences in tumor volume for the 210 to 260 mg/kg group compared with the control group on days 29 and 57 showed growth inhibited by 43% and 55%, respectively. At the same time, growth of SR DU145 xenografts generally was not slowed by suramin treatment at ally dose, but appeared to be enhanced to some degree by all doses of suramin during the typical slower initial growth phase of xenografts of this cell line: differences in tumor volume compared with control on day 29 showed growth enhanced by 100% to 342%. Mice treated with 210 to 260 mg/kg maintained nadir suramin plasma levels near our clinically relevant target of 1 x 10(-4) M. Conclusions: Suramin, without concomitant corticosteroid therapy, was effective in slowing the growth of DU145 xenografts in nude mice at clinically relevant plasma suramin levels, The data showing efficacy for DU145 xenografts was supported by the lack of efficacy at the same time for xenografts of cells known to be less responsive to suramin in vitro, i.e. the SR DU145 cells, at similar doses and nadir plasma suramin levels, In discussions on the utility of suramin our data should be considered as support for continuing the study of suramin in the treatment of advanced, androgen-independent prostate cancer.