磁机械应力诱导的结肠癌癌症细胞生长抑制

K. Spyridopoulou, Georgios Aindelis, C. Sarafidis, O. Kalogirou, K. Chlichlia
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摘要

在癌症研究领域,利用低频磁场驱动的内部磁性纳米颗粒(MNPs)在细胞中应用磁机械应力已经引起了相当大的兴趣。最近的发展证明磁机械应力可以抑制癌症细胞的生长。然而,MNP的类型和磁场的特性是至关重要的参数。它们的变异性允许多种组合,从而诱导特定的生物效应。我们之前报道了静止磁场(200mT)驱动的球形MNP(100nm)在HT29结肠癌癌症细胞中诱导的抗增殖作用。在此,我们发现在其他结肠癌癌症细胞系中也诱导了类似的生长抑制作用。磁机械应力对肿瘤球体生长速率的影响也得到了检验。此外,我们还研究了与观察到的细胞生长抑制有关的生物学机制。在所采用的实验条件下,通过PI(碘化丙啶)染色分析未检测到细胞死亡。流式细胞术和Western blotting显示G2/M细胞周期阻滞可能介导其抗增殖作用。此外,发现MNPs位于溶酶体中,并且在经历磁机械应力的细胞中检测到溶酶体数量减少,这意味着内化的MNPs的机械激活可以诱导溶酶体膜破坏。值得注意的是,溶酶体酸性条件已被证明会影响MNPs的磁性,振动样品磁强计(VSM)分析证明了这一点。进一步研究所描述的磁机械应力与溶酶体靶向化疗药物的结合,可以为开发新的抗癌联合治疗方案奠定基础。
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Magnetomechanical Stress-Induced Colon Cancer Cell Growth Inhibition
The application of magnetomechanical stress in cells using internalized magnetic nanoparticles (MNPs) actuated by low-frequency magnetic fields has been attracting considerable interest in the field of cancer research. Recent developments prove that magnetomechanical stress can inhibit cancer cells’ growth. However, the MNPs’ type and the magnetic field’s characteristics are crucial parameters. Their variability allows multiple combinations, which induce specific biological effects. We previously reported the antiproliferative effects induced in HT29 colon cancer cells by static-magnetic-field (200 mT)-actuated spherical MNPs (100 nm). Herein, we show that similar growth inhibitory effects are induced in other colon cancer cell lines. The effect of magnetomechanical stress was also examined in the growth rate of tumor spheroids. Moreover, we examined the biological mechanisms involved in the observed cell growth inhibition. Under the experimental conditions employed, no cell death was detected by PI (propidium iodide) staining analysis. Flow cytometry and Western blotting revealed that G2/M cell cycle arrest might mediate the antiproliferative effects. Furthermore, MNPs were found to locate in the lysosomes, and a decreased number of lysosomes was detected in cells that had undergone magnetomechanical stress, implying that the mechanical activation of the internalized MNPs could induce lysosome membrane disruption. Of note, the lysosomal acidic conditions were proven to affect the MNPs’ magnetic properties, evidenced by vibrating sample magnetometry (VSM) analysis. Further research on the combination of the described magnetomechanical stress with lysosome-targeting chemotherapeutic drugs could lay the groundwork for the development of novel anticancer combination treatment schemes.
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