Electroporation of LPB sarcoma cells in vitro and tumors in vivo increases the radiosensitizing effect of cisplatin.
BACKGROUND
Cisplatin is a cytotoxic drug with radiosensitizing effect. In this study a physical drug delivery system, electroporation, was used to facilitate cisplatin delivery into the cells and tumors with the aim of increasing radiation response.


METHODS
LPB murine sarcoma cells and tumors were treated either by cisplatin, electroporation or ionizing radiation, and combinations of these. In vitro radiation response was determined by colony forming assay while in vivo treatment effectiveness was determined by local tumor control (TCD50). Platinum accumulation in tumors by atomic absorption spectrometry and tumor perfusion changes by Patent blue staining were determined to elucidate some underlying antitumor mechanisms.


RESULTS
Exposure of cells in vitro to a combination of cisplatin and electroporation followed by irradiation increased the radiosensitizing effect of cisplatin. Also, the tumor radiocurability of this combined treatment was significantly enhanced, compared to irradiated tumors (enhancement factor; EF = 1.6) and to tumors treated with cisplatin and irradiation (EF = 1.4). Application of electric pulses to the tumors resulted in increased and prolonged accumulation of cisplatin and reduced tumor perfusion.


CONCLUSIONS
This study demonstrated that electroporation of cells and tumors increases the radiosensitizing effect of cisplatin, and that the predominant underlying mechanism is increased platinum delivery into the tumors due to the electroporation.
Kranjc
Simona
S
Institute of Oncology, Laboratory of Radiation Biology, Zaloska 2, SI-1000 Ljubljana, Slovenia.
Cemazar
Maja
M
Grosel
Alenka
A
Scancar
Janez
J
Sersa
Gregor
G
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D018274:Electroporation / Q000379:methods*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*
D011838:Radiation-Sensitizing Agents; D002945:Cisplatin