Experimental Studies on Killing and Inhibiting Effects of Steep Pulsed Electric Field (SPEF) to Target Cancer Cell and Solid Tumor

Abstract

Electroporation (i.e., reversible electrical breakdown) has been used for biomedicine such as electroporation therapy, transdermal drug delivery, cellular drug carrier systems, and gene transfer therapy. However, little research on the biological effect of irreversible electrical breakdown has been published. In this paper, the killing and inhibiting effects of pulsed electric field, whose rising edge is 100 ns level (we call it steep pulsed electric field, SPEF), to target cancer cell and solid tumor were successfully observed. The SPEF consists of two parts: the rising process containing ample high-frequency components, and the falling process containing lots of low-frequency components. Cell exposed to the pulse presented multiple changes: destructed membrane, swollen nucleus, disintegrated karyotheca, and cavitated, swollen mitochondria in histological and ultrastructure observations. SPEF blocked cell transition from G0/G1 phase to S+G2/M phase in flow cytometry analysis, and tumor growth retardation was observed in tumor-bearing mice. These experimental results show SPEF have a certain function to generate irreversible electrical breakdown in tumor cells, and might provide a new promising therapeutic approach for tumor treatment.