Electroporation enhances mitomycin C cytotoxicity on T24 bladder cancer cell line: A potential improvement of intravesical chemotherapy in bladder cancer

Intravesical mitomycin instillation combined with electric pulses is being used experimentally for the treatment of T1 bladder tumors, in patients unfit for surgery. Electroporation may enhance the uptake of chemotherapeutics by permeabilization of cell membranes. We investigated if electroporation improves the cytotoxicity of mitomycin. In two cell lines, T24 (bladder cancer cell line) and DC3F (Chinese hamster fibroblast), exposure to different concentrations of mitomycin (0.01-2000 mu M) was tested with and without electroporation (6 pulses of 1 kV/cm, duration: 99 mu s, frequency: 1 Hz). Cell viability was assessed by colorimetric assay (MTT). For both cell lines, mitomycin's IC_50 was approximately 1000 mu M in both pulsed and unpulsed cells. On T24 cells, electroporation and mitomycin caused (relative reduction) RR of survival of: 25%, 31% and 29%, by concentrations 0 mu M, 500 mu M and 1000 mu M respectively. For DC3F cells, the RRs of survival were: 28%, 29%, and 33%, by concentrations 0 mu M, 500 mu M and 1000 mu M respectively. In conclusion, electroporation and mitomycin together are about 30% more effective than mitomycin alone. The results help to elucidate the additive effect of mitomycin and electric pulses and support the use of this combination in the treatment of bladder cancer. (C) 2012 Elsevier B.V. All rights reserved.