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.C12 cells and their cisplatin-resistant subclone TBL.C12 Pt, which can be grown as in vitro cell cultures and as solid subcutaneous tumours in C57B1/6 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.C12 Pt cells were equally sensitive to electrochemotherapy us 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. (C) 2001 Elsevier Science Ltd. All rights reserved.