College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, People's Republic of China.
Biosens Bioelectron. 2009 Dec 15;25(4):721-7. doi: 10.1016/j.bios.2009.08.011. Epub 2009 Aug 15.
Integrity of the cell membrane is a basic requirement for maintaining the biological characteristics of a cell. In this study, changes in the morphology and ultrastructure of HeLa (human cervical carcinoma), HepG2 (human hepatocellular liver carcinoma), and C6 (rat glioma) cells were studied by atomic force microscopy (AFM) both before and after treatment with the anti-cancer drugs, colchicine or cytarabine. In response to both drugs, the microstructure of the cell membrane of all three cell types displayed similar changes; that is, with increases in drug concentration and reaction time, the degree of morphological changes on the surface of cell membrane increased. These changes included increases in the fluctuation of the surface components of the cell membrane, increase in shrinkage, or even the appearance of pores. Cell viability was maintained, as determined by optical microscope observation of gross cell morphology and by MTT assay results. Analysis of the cell membrane root-mean-square (RMS) roughness showed that under the action of colchicine and cytarabine, RMS values for the cell membranes of all three tumor cell types were positively correlated to the drug concentration and reaction time. This research has great significance for the visual diagnosis of early stage apoptosis in tumor cells in response to anti-cancer drugs, as well as in the studies on the interaction between drugs and cells. The use of AFM can be a rapid and sensitive visual method for studying the interaction between cells and drug.
细胞膜的完整性是维持细胞生物学特性的基本要求。本研究采用原子力显微镜（AFM）观察了秋水仙碱或阿糖胞苷作用前后宫颈癌 HeLa 细胞、肝癌 HepG2 细胞和大鼠胶质瘤 C6 细胞形态和超微结构的变化。对于这两种药物，三种细胞类型的细胞膜微观结构都显示出相似的变化；即随着药物浓度和反应时间的增加，细胞膜表面形态变化的程度增加。这些变化包括细胞膜表面成分的波动增加、收缩增加，甚至出现孔。光学显微镜观察细胞形态的总体和 MTT 检测结果表明细胞活力得以维持。细胞膜均方根（RMS）粗糙度分析表明，在秋水仙碱和阿糖胞苷的作用下，三种肿瘤细胞系的细胞膜 RMS 值与药物浓度和反应时间呈正相关。这项研究对于可视化诊断肿瘤细胞对抗癌药物的早期凋亡具有重要意义，也为药物与细胞相互作用的研究提供了依据。AFM 的应用可以作为一种快速、灵敏的观察细胞与药物相互作用的方法。
