Nanosecond electric pulses are equally effective in electrochemotherapy with cisplatin as microsecond pulses

纳秒电脉冲在顺铂电化学治疗中与微秒脉冲同样有效

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作者:Angelika Vizintin, Stefan Markovic, Janez Scancar, Jerneja Kladnik, Iztok Turel, Damijan Miklavcic

Background

Nanosecond electric pulses showed promising

Conclusions

Equivalent nanosecond pulses are equally effective in electrochemotherapy as standardly used 8 × 100 μs pulses.

Methods

Chinese hamster ovary CHO and mouse melanoma B16F1 cells were exposed to 1 × 200 ns pulse at 12.6 kV/cm or 25 × 400 ns pulses at 3.9 kV/cm, 10 Hz repetition rate or 8 × 100 μs pulses at 1.1 (CHO) or 0.9 (B16F1) kV/cm, 1 Hz repetition rate at three cisplatin concentrations. Cell survival was determined by the clonogenic assay, cellular platinum was measured by inductively coupled plasma mass spectrometry. Effects on the structure of cisplatin were investigated by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

Results

Nanosecond pulses equivalent to 8 × 100 μs pulses were established in vitro based on membrane permeabilization and cell survival. Equivalent nanosecond pulses were equally efficient in decreasing the cell survival and accumulating cisplatin intracellularly as 8 × 100 μs pulses after electrochemotherapy. The number of intracellular cisplatin molecules strongly correlates with cell survival for B16F1 cells, but less for CHO cells, implying the possible involvement of other mechanisms in electrochemotherapy. The high-voltage electric pulses did not alter the structure of cisplatin. Conclusions: Equivalent nanosecond pulses are equally effective in electrochemotherapy as standardly used 8 × 100 μs pulses.

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