Low-dose suramin enhances antitumor activity of mitomycin C in bladder tumors

2002 Our laboratory has reported that acidic and basic fibroblast growth factors (aFGF and bFGF) induce broad-spectrum resistance to anti-cancer drugs with diverse chemical structures and action mechanisms. We further found that low-dose suramin, a nonspecific inhibitor of FGF, enhances the activity of chemotherapeutic agents (paclitaxel, doxorubicin, 5-fluorouracil, CPT-11) in human tumors in vitro and in vivo. The present study evaluated whether low-dose suramin can enhance the activity of mitomycin C (MMC) in human bladder RT4 xenograft tumors and patient tumor histocultures. Well-established subcutaneous RT4 tumors implanted in immunodeficient mice were treated by intraperitoneal injections of physiologic saline, MMC (3 mg/kg), suramin (10 mg/kg), or combined MMC and suramin, twice weekly. Two schedules were studied. One schedule used 6 MMC treatments (referred to as therapeutic schedule) and the other used 3 treatments (subtherapeutic schedule). At the end of the treatments, tumors in the saline and suramin control groups increased to 3 and 4 times their initial sizes in 3- and 6-treatment groups, respectively. The therapeutic MMC schedule reduced the tumor size by 28% (p in vitro histoculture studies in patient bladder tumors indicated sensitization to MMC by 25 μM suramin, causing ∼4 fold decline in IC 50 of MMC. In summary, low-dose suramin enhanced the activity of subtherapeutic and therapeutic MMC schedules in bladder cancer. R37CA49816, NCI, DHHS.