ABSTRACT

Cell membrane acts as a barrier to the entry of impermeable drugs into cells. Recent studies have suggested that using magnetic fields can enable molecules to overcome the cell membrane barrier. However, the mechanism of membrane permeabilization remains unclear. Therefore, we evaluated the increases in bleomycin (CT) uptake, a non-permanent chemotherapy agent, using high-pulsed magnetic fields and investigated whether endocytosis was involved in the process. This study exposed MCF-7 cells to magnetic fields (2.2 T strength, different number of 28 and 56 pulses, and frequency of 1 and 10 Hz) in order to investigate whether this approach could promote the cell-killing efficiency of bleomycin. The involvement of endocytosis as a possible mechanism was tested by exposing cells to three endocytosis inhibitors, namely chlorpromazine, genistein, and amiloride. Our results illustrated that magnetic fields, depending on their conditions, could induce different endocytosis pathways. In such conditions as 10 Hz-28 pulses, 10 Hz-56 pulses, and 1 Hz-56 pulse, clathrin-mediated endocytosis was observed. Moreover, macropinocytosis was induced by the 10 Hz magnetic field and caveolae-mediated endocytosis occurred in all the magnetic field conditions. The findings imply that high-pulsed magnetic fields generate different endocytosis pathways in the MCF-7 cells, thus increasing the efficiency of chemotherapy agents.

摘要

细胞膜充当不可渗透药物进入细胞的屏障。最近的研究表明，使用磁场可以使分子克服细胞膜屏障。然而，膜透化的机制仍不清楚。因此，我们使用高脉冲磁场评估了非永久性化疗药物博来霉素 (CT) 摄取的增加，并研究了内吞作用是否参与该过程。本研究将 MCF-7 细胞暴露于磁场（2.2 T 强度，不同数量的 28 和 56 脉冲，频率为 1 和 10 Hz）以研究这种方法是否可以提高博来霉素的细胞杀伤效率。通过将细胞暴露于三种内吞作用抑制剂，即氯丙嗪、染料木素、和阿米洛利。我们的结果表明，磁场，根据它们的条件，可以诱导不同的内吞途径。在 10 Hz-28 脉冲、10 Hz-56 脉冲和 1 Hz-56 脉冲等条件下，观察到网格蛋白介导的内吞作用。此外，巨胞饮作用是由 10 Hz 磁场诱导的，并且在所有磁场条件下都发生了小窝介导的内吞作用。这些发现意味着高脉冲磁场在 MCF-7 细胞中产生不同的内吞作用途径，从而提高化疗药物的效率。巨胞饮作用是由 10 Hz 磁场诱导的，并且在所有磁场条件下都发生了小窝介导的内吞作用。这些发现意味着高脉冲磁场在 MCF-7 细胞中产生不同的内吞作用途径，从而提高化疗药物的效率。巨胞饮作用是由 10 Hz 磁场诱导的，并且在所有磁场条件下都发生了小窝介导的内吞作用。这些发现意味着高脉冲磁场在 MCF-7 细胞中产生不同的内吞作用途径，从而提高化疗药物的效率。