The Evidence of the Bystander Effect after Bleomycin Electrotransfer and Irreversible Electroporation.

Paulius Ruzgys,Jurij Novickij,Vitalij Novickij,Saulius Šatkauskas,Neringa Barauskaitė

doi:10.3390/molecules26196001

Paulius Ruzgys, Jurij Novickij + Show 3 more

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https://doi.org/10.3390/molecules26196001

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Abstract

One of current applications of electroporation is electrochemotherapy and electroablation for local cancer treatment. Both of these electroporation modalities share some similarities with radiation therapy, one of which could be the bystander effect. In this study, we aimed to investigate the role of the bystander effect following these electroporation-based treatments. During direct CHO-K1 cell treatment, cells were electroporated using one 100 µs duration square wave electric pulse at 1400 V/cm (for bleomycin electrotransfer) or 2800 V/cm (for irreversible electroporation). To evaluate the bystander effect, the medium was taken from directly treated cells after 24 h incubation and applied on unaffected cells. Six days after the treatment, cell viability and colony sizes were evaluated using the cell colony formation assay. The results showed that the bystander effect after bleomycin electrotransfer had a strong negative impact on cell viability and cell colony size, which decreased to 2.8% and 23.1%, respectively. On the contrary, irreversible electroporation induced a strong positive bystander effect on cell viability, which increased to 149.3%. In conclusion, the results presented may serve as a platform for further analysis of the bystander effect after electroporation-based therapies and may ultimately lead to refined application of these therapies in clinics.

Highlights

Enabled by more detailed characterization of new molecular tumor therapy features, facilitated and targeted drug delivery often is the desired option for tumor treatment [1].Among many physical and chemical targeted drug delivery methods, the electroporation technique has proved to be one of the most efficient, leading to its adoption in clinical practice [2,3,4]
Cells were treated with bleomycin or electric pulse and with a medium taken from untreated cells or cells treated with bleomycin or electric pulse
When the medium was taken from the control cells or cells treated with electric pulse or bleomycin and transferred to untreated cells, cell viability decreased to 72.35% ± 2.65%

Summary

Introduction

Enabled by more detailed characterization of new molecular tumor therapy features, facilitated and targeted drug delivery often is the desired option for tumor treatment [1].Among many physical and chemical targeted drug delivery methods, the electroporation technique has proved to be one of the most efficient, leading to its adoption in clinical practice [2,3,4]. Enabled by more detailed characterization of new molecular tumor therapy features, facilitated and targeted drug delivery often is the desired option for tumor treatment [1]. When the cellular transmembrane potential reaches the level of the electroporation threshold (in the range of 0.4 to 0.9 V), pores of a hydrophilic nature start forming in the cell plasma membrane [5]. This enables the diffusion of various exogenous molecules into the electroporated cells [6]. Bleomycin is the most frequently used anticancer drug for ECT, since electroporation of the selected areas of the tissue allows the use of this drug at a 1000 times lower concentration to trigger the desired killing effect [10]

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