Ciprofloxacin sensitizes hormone-refractory prostate cancer cell lines to doxorubicin and docetaxel treatment on a schedule-dependent manner.
OBJECTIVE
Combination therapy has generated a significant interest in the clinical setting since certain agents, with known mechanisms of action and non-overlapping toxicities may increase the therapeutic potential of anticancer drugs by decreasing systemic toxicity and overcoming drug resistance. Doxorubicin and docetaxel, two standard antineoplastic agents in hormone-refractory prostate cancer (HRPC) therapy and ciprofloxacin were evaluated singly and in several simultaneous and sequential drug combination schemes, against PC-3 and LNCaP cell lines.


METHODS
Cellular viability was determined by the resazurin assay and the assessment of synergism, additivity or antagonism was carried out by the median effect analysis. The importance of dose, exposure time and type of administration were investigated and compared.


RESULTS
Ciprofloxacin-doxorubicin or docetaxel combinations resulted in prominent additive or synergistic effects in both cell lines, when the cells were pre-treated with ciprofloxacin. These results suggest a rationale for dose reduction of doxorubicin and docetaxel in prostate cancer therapy, since the doses needed to achieve 50% cell death may be decreased by approximately 4- to 15-fold or 3- to 8-fold, respectively, after a pre-treatment with ciprofloxacin. In contrast, the referred combinations yielded moderate antagonistic effects when used concurrently in this in vitro system.


CONCLUSIONS
Ciprofloxacin sensitized HRPC cells to doxorubicin or docetaxel-induced growth inhibition and, therefore, may play a role as chemosensitizing agent in prostate cancer treatment.
Pinto
Ana Catarina
AC
Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
Moreira
João Nuno
JN
Simões
Sérgio
S
D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004336:Drug Antagonism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors
D000890:Anti-Infective Agents; D043823:Taxoids; D000077143:Docetaxel; D002939:Ciprofloxacin; D004317:Doxorubicin