Development of a statistical model for cervical cancer cell death with irreversible electroporation in vitro.

Yongji Yang,Edwin Zhang,Wenjun Zhang,Michael A J Moser,Bing Zhang,Aamir Ahmad

doi:10.1371/journal.pone.0195561

Abstract

PurposeThe aim of this study was to develop a statistical model for cell death by irreversible electroporation (IRE) and to show that the statistic model is more accurate than the electric field threshold model in the literature using cervical cancer cells in vitro.MethodsHeLa cell line was cultured and treated with different IRE protocols in order to obtain data for modeling the statistical relationship between the cell death and pulse-setting parameters. In total, 340 in vitro experiments were performed with a commercial IRE pulse system, including a pulse generator and an electric cuvette. Trypan blue staining technique was used to evaluate cell death after 4 hours of incubation following IRE treatment. Peleg-Fermi model was used in the study to build the statistical relationship using the cell viability data obtained from the in vitro experiments. A finite element model of IRE for the electric field distribution was also built. Comparison of ablation zones between the statistical model and electric threshold model (drawn from the finite element model) was used to show the accuracy of the proposed statistical model in the description of the ablation zone and its applicability in different pulse-setting parameters.ResultsThe statistical models describing the relationships between HeLa cell death and pulse length and the number of pulses, respectively, were built. The values of the curve fitting parameters were obtained using the Peleg-Fermi model for the treatment of cervical cancer with IRE. The difference in the ablation zone between the statistical model and the electric threshold model was also illustrated to show the accuracy of the proposed statistical model in the representation of ablation zone in IRE.ConclusionsThis study concluded that: (1) the proposed statistical model accurately described the ablation zone of IRE with cervical cancer cells, and was more accurate compared with the electric field model; (2) the proposed statistical model was able to estimate the value of electric field threshold for the computer simulation of IRE in the treatment of cervical cancer; and (3) the proposed statistical model was able to express the change in ablation zone with the change in pulse-setting parameters.

Highlights

Electroporation is defined as the creation of micro/nanopores in the cell membrane by transmembrane voltages leading to an increase in cell membrane permeability
The statistical models describing the relationships between Human cervical cancer (HeLa) cell death and pulse length and the number of pulses, respectively, were built
The difference in the ablation zone between the statistical model and the electric threshold model was illustrated to show the accuracy of the proposed statistical model in the representation of ablation zone in irreversible electroporation (IRE)

Summary

Introduction

Electroporation is defined as the creation of micro/nanopores in the cell membrane by transmembrane voltages leading to an increase in cell membrane permeability. Electroporation was used to treat tumors by creating reversible pores in the cell membranes of cancer cells, through which chemotherapeutic drug or plasmid DNA is delivered into intracellular structures to kill tumor cells—a process called electrochemotherapy (ECT) [1]. Based on ECT, Davalos et al proposed the idea of using irreversible pores in the cell membrane to kill tumor cells [2] (without chemotherapy), which has received much attention in the pre-clinical and clinical studies as a monotherapy for cancer treatment [3,4,5,6,7]. Unlike the case of ECT, the cell death that occurs in the process of IRE is due to the permanent membrane lysis and/or loss of homeostasis after the generation of irreversible pores in the cell membrane

Objectives

Methods

Results

Conclusion