In-vitro and in-vivo studies of the efficacy of electrochemotherapy for renal cell carcinoma

Abstract

Background. We aimed to assess a new approach to cancer therapy, using pulsed electric fields to facilitate the delivery of chemotherapeutic drugs. Methods. We investigated the cytotoxic effects on renal cell carcinoma of combinations of some well established anticancer drugs with electrical impulses, both in vitro and in vivo. The in-vivo study was done in nude mice bearing transplanted tumors. Results. In vitro, the treatments resulted in greater cytotoxic effects than either bleomycin (BLM) or high-voltage electrical impulses, alone. In renal cell carcinoma-bearing mice, the application of high-voltage electrical impulses to tumors, after the injection of BLM, resulted in disappearance of the tumors within 4 days. Such complete regression was achieved at a single BLM dose of 0.1 × lethal dose (LD)50, when combined with electrical in pulses. The tumors regrew after day 10, but at a much slower rate than at other concentrations of BLM. Other drugs used; cisplatin, 5-fluorouracil, mitomycin-C, and vinblastin, showed no retardation of tumor growth when compared with the results in “no-pulse” controls. The complete regression of tumors was associated with increased DNA cleavage and cell death. Conclusion. The concomitant use of high-voltage electrical impulses with BLM has the potential to increase the efficacy of BLM treatment of renal cancer, as reflected in substantial reduction in tumor growth.