Abstract

Glioblastoma (GBM) is one of the most aggressive cancer types in nervous system. Due to the limited effectiveness of current treatments, prognosis remains poor for GBM patients. Altered lipid metabolism is a hallmark of GBM. Previous studies show that increased lipid droplets (LDs) could protect cancer cells from chemotherapy and other extracellular stresses. In this study, we apply stimulated Raman scattering (SRS) microscopy to image LDs to monitor uptake of palmitic acid (PA) by U-87 glioma cells. We observe that uptake of free PA rapidly upregulates adipogenesis in glioma cells. We find that glioma cells exhibit distinctive time-dependent and dose-dependent patterns in PA uptake and adipogenesis. Uptake of extra PA significantly decreases the unsaturation degree of LDs. The decreased unsaturation degree and other lipotoxicity effects lead to clear cell death upon PA treatment at a high concentration. The results indicate that inhibition of adipogenesis may have therapeutic effects for GBM utilizing the lipotoxicity effects induced by free fatty acids. This work demonstrates that SRS microscopy for label-free imaging of LDs distribution and their composition is a promising tool for lipid metabolism studies in cancer.

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