Department of Biomedical Engineering, Binghamton University, State University of New York, Binghamton, NY, 13902, USA.
Department of Psychology, Binghamton University, State University of New York, Binghamton, NY, 13902, USA.
Sci Rep. 2021 Apr 1;11(1):7422. doi: 10.1038/s41598-021-86789-9.
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor. The effectiveness of traditional therapies for GBM is limited and therefore new therapies are highly desired. Previous studies show that lipid metabolism reprogramming may be a potential therapeutic target in GBM. This study aims to evaluate the therapeutic potential of free fatty acid-induced lipotoxicity for the suppression of glioma growth. U87 glioma cells are treated with three fatty acids (FAs): palmitic acid (PA), oleic acid (OA), and eicosapentaenoic acid (EPA). Uptake of the FAs and formation of lipid droplets (LDs) are imaged and quantified using a lab-built stimulated Raman scattering (SRS) microscope. Our results show that a supply of 200 µM PA, OA, and EPA leads to efficient LDs accumulation in glioma cells. We find that inhibition of triglycerides (TAGs) synthesis depletes LDs and enhances lipotoxicity, which is evidenced by the reduced cell proliferation rates. In particular, our results suggest that EPA treatment combined with depletion of LDs significantly reduces the survival rate of glioma cells by more than 50%, indicating the therapeutic potential of this approach. Future work will focus on understanding the metabolic mechanism of EPA-induced lipotoxicity to further enhance its anticancer effects.
多形性胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤。传统疗法治疗 GBM 的效果有限，因此非常需要新的疗法。先前的研究表明，脂代谢重编程可能是 GBM 的一个潜在治疗靶点。本研究旨在评估游离脂肪酸诱导的脂毒性对抑制神经胶质瘤生长的治疗潜力。用三种脂肪酸（FAs）：棕榈酸（PA）、油酸（OA）和二十碳五烯酸（EPA）处理 U87 神经胶质瘤细胞。使用实验室构建的受激拉曼散射（SRS）显微镜对 FAs 的摄取和脂滴（LDs）的形成进行成像和定量。我们的结果表明，供应 200μM 的 PA、OA 和 EPA 可导致神经胶质瘤细胞中 LDs 的有效积累。我们发现抑制甘油三酯（TAGs）的合成会耗尽 LDs 并增强脂毒性，这可以通过降低细胞增殖率来证明。特别是，我们的结果表明，EPA 处理与 LDs 的耗竭相结合，可使神经胶质瘤细胞的存活率降低 50%以上，表明该方法具有治疗潜力。未来的工作将集中于了解 EPA 诱导的脂毒性的代谢机制，以进一步增强其抗癌作用。
