Investigating the behavior of breast cancer cells via reaction kinetics may help unravel the mechanisms that underlie metabolic changes in tumors. However, obtaining human in vivo kinetic data is challenging because of difficulties associated with measuring these parameters. Nondestructive methods of measuring lipid content in live cells provide a novel approach to quantitatively model lipid synthesis and consumption. In this study, coherent Raman scattering microscopy was used to probe de novo intracellular lipid content. Combining nonlinear optical microscopy and Michaelis-Menten kinetics-based simulations, we isolated fatty acid synthesis/consumption rates and elucidated effects of altered lipid metabolism in T47D breast cancer cells. When treated with 17β-estradiol, the lipid utilization in cancer cells jumped by twofold. Meanwhile, the rate of de novo lipid synthesis in cancer cells treated with 17β-estradiol was increased by 42%. To test the model in extreme metabolic conditions, we treated T47D cells with etomoxir. Our kinetic analysis demonstrated that the rate of key enzymatic reactions dropped by 75%. These results underline the capability to probe lipid alterations in live cells with minimum interruption and to characterize lipid metabolism in breast cancer cells via quantitative kinetic models and parameters.

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通过非线性光学显微镜对乳腺癌细胞中脂质代谢的动力学分析

通过反应动力学研究乳腺癌细胞的行为可能有助于解开肿瘤代谢变化的基础机制。然而，由于与测量这些参数相关的困难，获得人体体内动力学数据具有挑战性。测量活细胞中脂质含量的无损方法提供了一种定量模拟脂质合成和消耗的新方法。在这项研究中，相干拉曼散射显微镜用于从头探测细胞内脂质含量。结合非线性光学显微镜和基于 Michaelis-Menten 动力学的模拟，我们分离了脂肪酸合成/消耗率，并阐明了 T47D 乳腺癌细胞中脂质代谢改变的影响。当用 17β-雌二醇处理时，癌细胞中的脂质利用率增加了两倍。同时，用 17β-雌二醇处理的癌细胞从头合成脂质的速度增加了 42%。为了在极端代谢条件下测试模型，我们用 etomoxir 处理了 T47D 细胞。我们的动力学分析表明，关键酶促反应的速率下降了 75%。这些结果强调了在最小中断的情况下探测活细胞中脂质变化的能力，并通过定量动力学模型和参数表征乳腺癌细胞中的脂质代谢。