Delivery of low intensity/low frequency electric fields via clinical Deep Brain Stimulation electrodes has anti-proliferative effects on Glioblastoma multiforme cell lines

Abstract

INTRODUCTION

Phase III trials of Tumour Treating Fields (TTFields) have shown potentially positive results in both primary and recurrent adult Glioblastoma multiforme (GBM), giving hope that electric fields present a new treatment paradigm for brain tumours. Here we present investigations into the repurposing of deep brain stimulation (DBS) electrodes as a novel delivery method of therapeutic electric fields to high grade brain tumours as a localised, and internalised system.

METHODS

Medtronic DBS electrodes were inserted into cell culture flasks and delivered electric fields over a range of voltages and frequencies to a panel of primary, adult and paediatric GBM cell lines. Cell viability, cell count, cell cycle analyses, as well as combinational studies with an array of mitotic inhibitors were undertaken.

RESULTS

DBS electric fields negatively affect cell counts and viabilities of GBM cells. Cell viability was reduced by up to 70% in U87, 74% in SF188, 71% in KNS42 and 45% in GIN-5 cell lines in a voltage-dependent manner The influence of frequency on cell viability is also demonstrated. Cell counts were undertaken of treated flasks and compared across all intensities. Cell cycle analysis performed via flow cytometry reveals that electrotreatment significantly increases the proportion of cells in G0 phase relative to control flasks in GBM cells. The effects of electrotreatment in combination with mitotic inhibitors are also explored.

CONCLUSIONS

Implantable DBS electrodes have potential as a localised electric field based therapeutic strategy for the treatment of brain tumours. Electric fields delivered from DBS electrodes at significantly lower frequencies and intensities than those utilised by OptuneTM have profound anti-proliferative effects on GBM cell lines, causing measurable alterations in cell cycling. Impact: Implantable multiple DBS electrodes may address the compliance issues associated with Optune and provide a new modality for loco-regional brain tumour treatment.