Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Minin and Pozharsky Square, 10/1, 603005 Nizhny Novgorod, Russia.
N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Kosygin st. 4, 119991 Moscow, Russia.
Int J Mol Sci. 2023 Jul 29;24(15):12186. doi: 10.3390/ijms241512186.
The cell membrane is an important regulator for the cytotoxicity of chemotherapeutic agents. However, the biochemical and biophysical effects that occur in the membrane under the action of chemotherapy drugs are not fully described. In the present study, changes in the microviscosity of membranes of living HeLa-Kyoto tumor cells were studied during chemotherapy with paclitaxel, a widely used antimicrotubule agent. To visualize the microviscosity of the membranes, fluorescence lifetime imaging microscopy (FLIM) with a BODIPY 2 fluorescent molecular rotor was used. The lipid profile of the membranes was assessed using time-of-flight secondary ion mass spectrometry ToF-SIMS. A significant, steady-state decrease in the microviscosity of membranes, both in cell monolayers and in tumor spheroids, was revealed after the treatment. Mass spectrometry showed an increase in the unsaturated fatty acid content in treated cell membranes, which may explain, at least partially, their low microviscosity. These results indicate the involvement of membrane microviscosity in the response of tumor cells to paclitaxel treatment.
细胞膜是化疗药物细胞毒性的重要调节剂。然而，化疗药物作用下膜中发生的生化和生物物理效应尚未得到充分描述。在本研究中，我们研究了广泛使用的抗微管药物紫杉醇化疗过程中活 HeLa-Kyoto 肿瘤细胞膜的微粘度变化。为了可视化膜的微粘度，我们使用带有 BODIPY 2 荧光分子转子的荧光寿命成像显微镜（FLIM）进行了研究。使用飞行时间二次离子质谱法（ToF-SIMS）评估了膜的脂质分布。结果显示，在单层细胞和肿瘤球体处理后，膜的微粘度均显著且稳定地降低。质谱分析显示，处理后的细胞膜中不饱和脂肪酸含量增加，这至少可以部分解释其低微粘度。这些结果表明，膜微粘度参与了肿瘤细胞对紫杉醇治疗的反应。
