Abstract 203: Single cell imaging of kinase inhibitor-induced effects in breast cancer cell lines

Abstract

Abstract There is need for improved targeted therapies for the treatment of breast cancer. Kinase inhibitors are candidates to be used in this context. With the goal of uncovering specific vulnerabilities in differing cell lines, we treated five breast cancer cell lines representing triple negative (BT20, MDAMB231, and Hs578T), hormone receptor positive (MCF7), and Her2 amplified (SKBR3) disease and the non-malignant MCF10A line with a panel of 105 kinase inhibitors covering a broad range of targets. Cells were treated with doses between 0.1 and 10 μM for 24 hours, at which time they were stained with DRAQ5 (DNA) and TMRE (mitochondrial membrane potential). Live-cell images were acquired using a high throughput, confocal Opera microscope. Cell segmentation, based on the DRAQ5 staining, and feature extraction (intensity, morphology, and texture) were performed with Acapella software. Over 300 features were extracted for ∼1.5 million cells. Analytical methods have been applied to identify those treatments that induced significant changes to the cells. Over half of the kinase inhibitors queried had a significant effect within 24 hours in all cell lines at 10 μM. Cell cycle inhibitors had the most common effects across cell lines. Cell line specific effects were also uncovered, for example, MDAMB231 cells were the most sensitive to MAPK inhibitors. These, early time point, results have been compared with the effects of the same inhibitors on cell growth to better understand the mechanisms leading to cell line and pathway specific effects. Citation Format: Caitlin Mills, David Andrews, Peter Sorger. Single cell imaging of kinase inhibitor-induced effects in breast cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 203.