Enhancement of antitumor effect of bleomycin by low-voltage in vivo electroporation: A study of human uterine leiomyosarcomas in nude mice

Uterine leiomyosarcoma is an extremely malignant neoplasm with high rates o f distant metastasis, and systemic chemotherapy is not particularly effecti ve. Thus, the introduction of more active anticancer agents, or of a new dr ug delivery system, is urgently needed, Recently, electrochemotherapy has b een introduced as a way of enhancing the cytotoxic effects of chemotherapeu tic agents. This involves administering the drug in combination with electr ic pulses (which permeabilize tumor cell membranes and allow the drug to en ter the cells). In particular, bleomycin (BLM) cannot cross the plasma memb rane efficiently, but its cytotoxicity can be enhanced by electropermeabili zation. The aim of the present study was to investigate the effect of low-v oltage electroporation (EP) in combination with local BLM injection on the growth of uterine leiomyosarcoma in nude mice. Human uterine leiomyosarcoma cells (SK-LMS-I) were implanted subcutaneously into nude mice. Tumor growt h in mice treated with EP (100 V/cm) plus BLM was compared with that in mic e receiving BLM alone, EP alone, or no treatment (controls), Tissue BLM con centrations and histological analysis (including mitotic counts) were evalu ated in tumor tissues. There was a significant reduction in tumor growth in mice that received EP with BLM, One hour after the treatment, the local BL M concentration was 10 times higher in the tumors that received EP with BLM than in those receiving only BLM, Moreover, the mitotic count was lower in the tumors that received EP plus BLM than in the controls. These results d emonstrate the possible therapeutic value of low-voltage EP with BLM in hum an uterine leiomyosarcoma, (C) 2000 Wiley-Liss. Inc.