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

Purpose: Toward developing a model to study the mechanism of action of sura min against prostate cancer, we identified the effect of suramin on the gro wth of xenografts of the androgen-independent human prostate carcinoma DU14 5 cell line and our subline of suramin-resistant (SR) DU145 cells which are less responsive to suramin in vitro, Methods: Athymic nude mice bearing DU 145 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 xenograft s was slowed by treatment with 210 to 260 mg/kg suramin IP once weekly: dif ferences in tumor volume for the 210 to 260 mg/kg group compared with the c ontrol group on days 29 and 57 showed growth inhibited by 43% and 55%, resp ectively. 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 s ome degree by all doses of suramin during the typical slower initial growth phase of xenografts of this cell line: differences in tumor volume compare d with control on day 29 showed growth enhanced by 100% to 342%. Mice treat ed with 210 to 260 mg/kg maintained nadir suramin plasma levels near our cl inically relevant target of 1 x 10(-4) M. Conclusions: Suramin, without con comitant corticosteroid therapy, was effective in slowing the growth of DU1 45 xenografts in nude mice at clinically relevant plasma suramin levels, Th e data showing efficacy for DU145 xenografts was supported by the lack of e fficacy at the same time for xenografts of cells known to be less responsiv e 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 sh ould be considered as support for continuing the study of suramin in the tr eatment of advanced, androgen-independent prostate cancer.