Tumor Growth Inhibited by Low-Voltage Amplitude and 5-kHz Frequency Electrochemotherapy

Abstract

The most important unpleasant sensation of electrochemotherapy is muscle contraction. One of the causes of this discomfort is electrochemotherapy in the low-frequency range (1Hz). To resolve this problem, there are two solutions: first, increasing the repetition frequency of electric pulses above the tetanic frequency and, second, reducing the voltage amplitude. This study examines the antitumor effectiveness of treatment using low electric fields and high frequency in the presence and absence of chemotherapeutic agents. High-voltage amplitude electrochemotherapy was performed by eight pulses, at 1,000V/cm, of 100-μs duration at 1-Hz and 5-kHz repetition frequency. In the low-voltage amplitude protocol, 4,000 pulses, of 100-μs duration at 5-kHz repetition frequency with 70, 100 and 150V/cm were delivered to invasive ductal carcinoma tumors after intratumoral injection of bleomycin. Our data demonstrate significant differences in tumor volumes and the curability rate between mice treated by 70V/cm compared to other groups. Electrochemotherapy, which is specified by a higher repetition frequency of electric pulses (5kHz) and low voltage, inhibits tumor growth. This protocol has a comparable effect to 1-Hz pulse repetition electric pulses with high voltage. Based on these results, the 4,000 pulses of 70V/cm with 5-kHz frequency are most effective. This protocol demonstrates inhibition of tumor growth without any need for drug administration.