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为弥补抗肿瘤活性评估常规断点检测法操作繁琐、灵敏度低等局限,尝试建立基于细胞动态生物反应谱的抗肿瘤先导化合物筛选新方法。依据活细胞具有电阻抗生物传感属性,以细胞指数、半数抑制浓度IC50和脱附曲线为评价指标,采用实时在线分析技术动态监测模式药表柔比星、顺铂、卡铂对HepG2细胞生长的影响,并辅以CCK-8(cell counting kit-8)和显微监视佐证。结果显示,以细胞指数-作用时间关系表征的细胞动态生物反应谱可灵敏地反映模式药抑制HepG2细胞的动态特征效应信息,3种药物的IC50分别为(0.53±0.04)、(9.79±0.26)和(597.00±3.79)μg·mL-1,进一步发现3种药物的脱附曲线差异明显,提示其作用特征可能不同,这与常规检测方法及文献报道一致。研究表明,具有无标记、非侵入、实时动态等特点的细胞动态生物反应谱技术,可定性定量地表征3种药物对HepG2细胞作用的过程动态信息,反映不同药物作用特征性差异,有望为抗肿瘤先导化合物的发现及作用特点或机制阐释提供线索。
In order to make up for antitumor activity, the conventional breakpoint detection method is cumbersome to operate and low in sensitivity, and a new method for screening of antitumor lead compounds based on the cellular dynamic biological response spectrum is attempted. According to the characteristics of living cells with electrical impedance, the cell index, IC50 and desorption curve were used as the evaluation indexes to monitor the growth of HepG2 cells by using real-time on-line analytical technique. And supplemented by CCK-8 (cell counting kit-8) and micro-monitoring evidence. The results showed that the cell dynamic response spectrum characterized by cell index - time relationship could sensitively reflect the dynamic characteristic information of HepG2 cells inhibited by model drugs. The IC50 values of the three drugs were (0.53 ± 0.04) and (9.79 ± 0.26) And (597.00 ± 3.79) μg · mL-1, respectively. It was further found that the desorption curves of the three drugs showed significant differences, suggesting that the characteristics of the three drugs may be different. This is consistent with the conventional detection methods and reported in the literature. The research shows that dynamic cell response spectrum technology with characteristics of non-marking, non-invasive and real-time dynamic can qualitatively and quantitatively characterize the process dynamics of three drugs on HepG2 cells and reflect the characteristic differences of different drugs and is expected to be resistant Tumor lead compounds found in the characteristics and mechanism of action or provide clues.