Electrochemotherapy of tumours resistant to cisplatin: a study in a murine tumour model.
The aim of the study was to determine whether electrochemotherapy with cisplatin could be implemented in treatment of cisplatin-resistant solid tumours. For this purpose, we used cisplatin-sensitive TBL.Cl2 cells and their cisplatin-resistant subclone TBL.Cl2 Pt, which can be grown as in vitro cell cultures and as solid subcutaneous tumours in C57Bl/6 mice. Cytotoxicity of cisplatin alone and combined with electroporation was determined by colony forming assay. Treatment effects of electrochemotherapy in vivo were assessed by tumour growth delay and tumour curability. Platinum content in the cells and tumours was determined by atomic absorption spectroscopy. In vitro, TBL.Cl2 Pt cells were equally sensitive to electrochemotherapy as their cisplatin-sensitive counterparts. In vivo, electrochemotherapy was effective on both tumour types, resulting in a prolonged tumour growth delay and tumour cures. However, electrochemotherapy was more effective on parental than cisplatin-resistant tumours, in which platinum content was significantly lower compared with parental tumours. In conclusion, electrochemotherapy is an effective treatment of cisplatin-resistant solid tumours and may prove useful in clinical chemotherapy for the treatment of tumours with intrinsic or acquired resistance to cisplatin.
Cemazar
M
M
Department of Tumor Biology, Institute of Oncology, Zaloska 2, SI-1000, Ljubljana, Slovenia. mcemazar@onko-i.si
Miklavcic
D
D
Mir
L M
LM
Belehradek
J
J
Bonnay
M
M
Fourcault
D
D
Sersa
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D007262:Infusions, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012509:Sarcoma / Q000188:drug therapy*
D000970:Antineoplastic Agents; D002945:Cisplatin