Breast cancer cell obatoclax response characterization using passivated-electrode insulator-based dielectrophoresis

Abstract

Inherent electrical properties of cells can be beneficial to characterize different cell lines and their response to experimental drugs. This paper presents a novel method to characterize the response of breast cancer cells to drug stimuli through use of off-chip passivated-electrode insulator-based dielectrophoresis (OπDEP) and the application of AC electric fields. This work is the first to demonstrate the ability of OπDEP to differentiate between two closely related breast cancer cell lines, LCC1 and LCC9 while assessing their drug sensitivity to an experimental anti-cancer agent, Obatoclax. Although both cell lines are derivatives of estrogen-responsive MCF-7 breast cancer cells, growth of LCC1 is estrogen independent and anti-estrogen responsive, while LCC9 is both estrogen-independent and anti-estrogen resistant. Under the same operating conditions, LCC1 and LCC9 had different DEP profiles. LCC1 cells had a trapping onset (crossover) frequency of 700 kHz and trapping efficiencies between 30-40%, while LCC9 cells had a lower crossover frequency (100 kHz) and showed higher trapping efficiencies of 40-60%. When exposed to the Obatoclax, both cell lines exhibited dose-dependent shifts in DEP crossover frequency and trapping efficiency. Here, DEP results supplemented with cell morphology and proliferation assays help us to understand the response of these breast cancer cells to Obatoclax.

Keywords: Breast cancer; Dielectrophoresis (DEP); Drug sensitivity; Estrogen receptor positive (ER+); GX15-070 (Obatoclax).

Figure 1

(A) Top view of the fabricated microfluidic chip and electrodes. The image shows the alignments of the microfluidic device with the DEP pillars positions directly above and in-between the reusable (detachable) electrodes spaced 400 µm. (B) Close-up of the DEP pillars within the microfluidic chip and electrodes that lie below the microfluidic chip and surround the DEP pillars.

Figure 2

Proliferation assay results for untreated and 500 nM GX-treated LCC1 and LLC9 cells under control conditions (DMSO vehicle alone) at 12, 24, and 48 h.

Figure 3

Trapping profile of vehicle and GX-treated at 100 nM, 500 nM, and 1 µM (A) LCC1 and (B) LCC9 cells, each bar represents mean ± standard error of mean for at least three experiments (n> = 3).

Figure 4

SEM images of vehicle control and 500 nM GX-treated LCC1 and LCC9 cells with labeling below each image.