Electroporation enhances mitomycin C cytotoxicity on T24 bladder cancer cell line: A potential improvement of intravesical chemotherapy in bladder cancer
Vásquez JL, Gehl J, Hermann GG. Bioelectrochemistry. 2012 Aug 11;88C:127-133. [Epub ahead of print]

Source

Center for Drug and Gene Electrotransfer, Department of Oncology 54B1, Copenhagen University Hospital Herlev, Herlev Ringvej 75, 2730 Herlev, Denmark; Department of Urology, Copenhagen University Hospital Frederiksberg, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark; Department of Urology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.

Abstract

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 (0.01-2000μM) was tested with and without electroporation (6 pulses of 1kV/cm, duration: 99μs, frequency: 1Hz). Cell viability was assessed by colorimetric assay (MTT). For both cell lines, mitomycin's IC_50 was approximately 1000μM 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 0μM, 500μM and 1000μM respectively. For DC3F cells, the RRs of survival were: 28%, 29%, and 33%, by concentrations 0μM, 500μM and 1000μM 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.