Abstract
Statins have displayed significant, although heterogeneous, anti-tumour activity in breast cancer disease progression and recurrence. They offer promise as a class of drugs, normally used for cardiovascular disease control, that could have a significant impact on the treatment of cancer. Understanding their mode of action and accurately assessing their efficacy on live cancer cells is an important and significant challenge. Stimulated Raman scattering (SRS) microscopy is a powerful, label-free imaging technique that can rapidly characterise the biochemical responses of live cell populations following drug treatment. Here, we demonstrate multi-wavelength SRS imaging together with spectral phasor analysis to characterise a panel of breast cancer cell lines (MCF-7, SK-BR-3 and MDA-MB-231 cells) treated with two clinically relevant statins, atorvastatin and rosuvastatin. Label-free SRS imaging within the high wavenumber region of the Raman spectrum (2800–3050 cm−1) revealed the lipid droplet distribution throughout populations of live breast cancer cells using biocompatible imaging conditions. A spectral phasor analysis of the hyperspectral dataset enables rapid differentiation of discrete cellular compartments based on their intrinsic SRS characteristics. Applying the spectral phasor method to studying statin treated cells identified a lipid accumulating phenotype in cell populations which displayed the lowest sensitivity to statin treatment, whilst a weaker lipid accumulating phenotype was associated with a potent reduction in cell viability. This study provides an insight into potential resistance mechanisms of specific cancer cells towards treatment with statins. Label-free SRS imaging provides a novel and innovative technique for phenotypic assessment of drug-induced effects across different cellular populations and enables effective analysis of drug–cell interactions at the subcellular scale.
Highlights
Previous studies have used brightfield[7] and fluorescent microscopy[8] to visualise intracellular lipid dynamics associated with statin treatment in breast and pancreatic cancer cells, respectively
The aim for this research was to investigate if statin treatment would trigger a varying lipid profile as a consequence of altered lipid metabolism
Our results indicated that in serum-free media, cells which were treated with increasing atorvastatin concentrations resulted in lipid accumulation, at higher (>5 μM) concentrations (Figure S10A), whilst a weaker lipid accumulation effect was detected in the rosuvastatin treated cells (Figure S10B)
Summary
Previous studies have used brightfield[7] and fluorescent microscopy[8] to visualise intracellular lipid dynamics associated with statin treatment in breast and pancreatic cancer cells, respectively. We describe the application of SRS microscopy combined with a spectral phasor analysis for label-free characterisation of breast cancer cells exposed to increasing concentrations of two clinically relevant statins, atorvastatin and rosuvastatin.
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