Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice.
BACKGROUND
Bleomycin is poorly permeant but potent cytotoxic and radiosensitizing drug. The aim of the study was to evaluate whether a physical drug delivery system - electroporation can increase radiosensitising effect of bleomycin in vitro and in vivo.


METHODS
LPB sarcoma cells and tumors were treated either with bleomycin, electroporation or ionizing radiation, and combination of these treatments. In vitro, response to different treatments was determined by colony forming assay, while in vivo, treatment effectiveness was determined by local tumor control (TCD50). Time dependence of partial oxygen pressure in LPB tumors after application of electric pulses was measured by electron paramagnetic oxyimetry.


RESULTS
Electroporation of cells in vitro increased radiosensitising effect of bleomycin for 1.5 times, in vivo radiation response of tumors was enhanced by 1.9 fold compared to response of tumors that were irradiated only. Neither treatment of tumors with bleomycin nor application of electric pulses only, affected radiation response of tumors. Application of electric pulses to the tumors induced profound but transient reduction of tumor oxygenation. Although tumor oxygenation after electroporation partially restored at the time of irradiation, it was still reduced at the level of radiobiologically relevant hypoxia.


CONCLUSIONS
Our study shows that application of electric pulses to cells and tumors increases radiosensitising effect of bleomycin. Furthermore, our results demonstrate that the radiobiologically relevant hypoxia induced by electroporation of tumors did not counteract the pronounced radiosensitising effect of electrochemotherapy with bleomycin.
Kranjc
Simona
S
Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia. skranjc@onko-i.si
Cemazar
Maja
M
Grosel
Alenka
A
Sentjurc
Marjeta
M
Sersa
Gregor
G
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004578:Electron Spin Resonance Spectroscopy; D018274:Electroporation; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012509:Sarcoma / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
D011838:Radiation-Sensitizing Agents; D001761:Bleomycin; D010100:Oxygen