多烯紫杉醇诱导细胞周期阻断与凋亡过程的模型

Mathematical model for analysis of cell cycle arrest and apoptosis induced by docetaxel

以多烯紫杉醇诱导白血病细胞株K562为对象,建立了描述肿瘤细胞生长及其与药物作用关系的细胞周期数学模型,研究了多烯紫杉醇诱导K562细胞周期变化与凋亡现象及量效关系.结果表明,多烯紫杉醇引起K562细胞M期阻断和诱导细胞凋亡的饱和浓度分别为17.96、7.82 nmol·L-1,有效浓度分别为2.63、1.69 nmol·L-1;低浓度(1.69～2.63 nmol·L-1)的多烯紫杉醇直接诱导细胞凋亡而不引起明显的M期阻断;高浓度(>7.82 nmol·L-1)的多烯紫杉醇主要效应是促进细胞M期阻断.本模型揭示出M期阻断与凋亡无显著的相关性,为多烯紫杉醇的作用机制提供了一个新的解释.

A mathematical model of in vitro cancer cell growth differentiated by cell cycle distribution and antimitotic drug interaction was presented. The model was adapted to the growth and treatment of human leukemia K562 cells with docetaxel. It described docetaxel-induced apoptosis, G2/M phase arrest as well as the relationship of drug concentration and cell response manners. The model showed that the saturation docetaxel concentrations to cause M-phase arrest and apoptosis in K562 cells were 17.96 nmol&middotL-1 and 7.82 nmol&middotL-1 and the effective concentrations were 2.63 nmol&middotL-1 and 1.69 nmol&middotL-1, respectively. Low concentration docetaxel (1.69-2.63 nmol&middotL-1) induced apoptosis directly, without obvious M-phase arrest, while cells mainly reacted with concentration-dependent M-phase arrest and saturated apoptosis at high concentration docetaxel (> 7.82 nmol&middotL-1). The model indicated that M-phase arrest was not positively related to apoptosis, which gave a new explanation for the mechanism of docetaxel.