In Vitro Interaction of Cisplatin and Fosfomycin on Squamous Cell Carcinoma Cultures

Objective: Fosfomycin has been shown to be otoprotective and nephroprotective against cisplatin-induced toxic reactions. This study tests whether fosfomycin inhibits the anticancer effect of cisplatin. Methods: Three squamous cell carcinoma cell lines were used to determine the effect of fosfomycin on cisplatin-induced tumoricidal activity. Cells were grown in 96 well plates with fosfomycin alone, cisplatin alone, or fosfomycin and cisplatin together. Cell surivial was then measured by a colorimetric technique using 3-4,5-dimethylthiazol-2-yl 2,5 diphenyltetrazolium bromide (MTT). Results: There was no decrease in the effectiveness of cisplatin in killing human squamous cell carcinoma in vitro when fosfomycin was present in concentrations of up to 400 mg/L. One cell line also showed killing at high concentrations of cisplatin, but not at low concentrations. Conclusions: Fosfomycin protects against cisplatin-induced toxic reactions and does not inhibit tumoricidal activity in vitro. In addition, one cell line showed relative resistance to cisplatin at low doses, but was effectively killed with high doses of cisplatin. This is the ideal situation for use of fosfomycin so that higher doses of cisplatin may be given with renal and otologic protection.