常见抗生素对浅表性膀胱癌的抗肿瘤活性。

Antitumor activity of common antibiotics against superficial bladder cancer.

作者信息

Kamat Ashish M, Lamm Donald L

机构信息

Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Urology. 2004 Mar;63(3):457-60. doi: 10.1016/j.urology.2003.10.038.

DOI:10.1016/j.urology.2003.10.038

PMID:15028437

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 microg/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 microg/mL (HTB9, TccSup) and 50 microg/mL (T24) for ciprofloxacin, 31.25 microg/mL (HTB9, TccSup) and 62.5 microg/mL (T24) for trimethoprim-sulfamethoxazole, 19.5 microg/mL (HTB9) and 156.3 microg/mL (T24, TccSup) for cefazolin, and 7.8 microg/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.

摘要

目的

经完全切除治疗的浅表性膀胱肿瘤复发率平均为88%。膀胱内化疗仅使复发率降低14%；因此，需要新的化疗药物。抗生素常用于经尿道膀胱肿瘤切除术后预防感染。口服抗生素后尿液中的浓度显著高于血清中的浓度。我们的目的是评估四种常用的尿路抗生素在临床相关浓度下对膀胱癌细胞的细胞毒性活性。

方法

将三种人移行细胞癌系——HTB9（2级）、T24（3级）和TccSup（4级）——分别暴露于环丙沙星、甲氧苄啶-磺胺甲恶唑、头孢唑林或呋喃妥因，浓度分别为0（对照）至1000、1000、5000和2000μg/mL，持续96小时。使用MTT比色法评估细胞毒性。每个数据点使用六个复制品，结果报告为平均值±标准差。

结果

环丙沙星在浓度为12.5μg/mL（HTB9、TccSup）和50μg/mL（T24）时，甲氧苄啶-磺胺甲恶唑在31.25μg/mL（HTB9、TccSup）和62.5μg/mL（T24）时，头孢唑林在19.5μg/mL（HTB9）和156.3μg/mL（T24、TccSup）时，呋喃妥因在7.8μg/mL（HTB9、T2&、TccSup）时均出现显著细胞毒性（P<0.001）。所有四种抗生素的细胞毒性均呈剂量依赖性，且最大效应在各抗生素之间无差异。