Antitumor activity of common antibiotics against superficial bladder cancer

Abstract

Objectives The recurrence rate for superficial bladder tumors treated with complete resection averages 88%. Intravesical chemotherapy decreases the recurrence rate by only 14%; thus, new chemotherapeutic agents are needed. Antibiotics are often used to prevent infections after transurethral resection of bladder tumors. Oral intake of antibiotics results in significantly greater concentrations in the urine than in the serum. Our objective was to evaluate four commonly used urinary antibiotics for their cytotoxic activity against bladder cancer cells at clinically relevant concentrations. Methods Three human transitional cell carcinoma lines—HTB9 (grade 2), T24 (grade 3), and TccSup (grade 4)—were exposed to ciprofloxacin, trimethoprim-sulfamethoxazole, cefazolin, or nitrofurantoin at concentrations from 0 (control) to 1000, 1000, 5000, and 2000 μg/mL, respectively, for 96 hours. Cytotoxicity was evaluated using the MTT colorimetric assay. Six replicates were used for each data point, and the results are reported as the mean ± standard deviation. Results Significant cytotoxicity ( P <0.001) was seen, starting at 12.5 μg/mL (HTB9, TccSup) and 50 μg/mL (T24) for ciprofloxacin, 31.25 μg/mL (HTB9, TccSup) and 62.5 μg/mL (T24) for trimethoprim-sulfamethoxazole, 19.5 μg/mL (HTB9) and 156.3 μg/mL (T24, TccSup) for cefazolin, and 7.8 μg/mL (HTB9, T24, TccSup) for nitrofurantoin. Cytotoxicity was dose dependent for all four antibiotics, and the maximal effect did not differ among antibiotics. Conclusions Commonly used antibiotics exhibit significant dose-dependent cytotoxicity against bladder cancer cells at concentrations achievable in the urine after oral administration. The administration of antibiotics after transurethral resection of bladder tumors might prevent seeding of cancer cells and thereby decrease the recurrence rate. Preclinical data such as these must be considered in the design of clinical trials addressing recurrence after transurethral resection of bladder tumors.