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首页> 美国卫生研究院文献>British Journal of Cancer >Differential cytotoxicity of 19 anticancer agents in wild type and etoposide resistant small cell lung cancer cell lines.
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Differential cytotoxicity of 19 anticancer agents in wild type and etoposide resistant small cell lung cancer cell lines.

机译：19种抗癌药在野生型和依托泊苷抗性小细胞肺癌细胞系中的差异细胞毒性。

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A panel of six 'wild type' and three VP-16 resistant small cell lung cancer (SCLC) cell lines is used to evaluate to what extent in vitro sensitivity testing using a clonogenic assay can contribute to combine cytotoxic drugs to regimens with improved efficacy against SCLC. The resistant lines include (a) H69/DAU4, which is classical multidrug resistant (MDR) with a P-glycoprotein efflux pump (b) NYH/VM, which exhibits an altered topoisomerase II (topo II) activity and (c) H69/VP, which is cross-resistant to vincristine, exhibits a reduced drug accumulation as H69/DAU4 but is without P-glycoprotein. 19 anticancer agents were compared in the panel. The MDR lines demonstrated, as expected, cross-resistance to all topo II drugs, but also different patterns of collateral sensitivity to BCNU, cisplatin, ara-C, hydroxyurea, and to the topo I inhibitor camptothecin. The complete panel of nine cell lines clearly demonstrated diverse sensitivity patterns to drugs with different modes of action. Correlation analysis showed high correlation coefficients (CC) among drug analogues (e.g. VP-16/VM-26 0.99, vincristine/vindesine 0.89), and between drugs with similar mechanisms of action (e.g. BCNU/Cisplatin 0.89, VP-16/Doxorubicin 0.92), whereas different drug classes demonstrated low or even negative CC (e.g. BCNU/VP-16 -0.21). When the CC of the 19 drug patterns to VP-16 were plotted against the CC to BCNU, clustering was observed between drugs acting on microtubules, on topo II, alkylating agents, and antimetabolites. In this plot, camptothecin and ara-C patterns were promising by virtue of their lack of cross-resistance to alkylating agents and topo II drugs. Thus, the differential cytotoxicity patterns on this panel of cells can (1) give information about drug mechanism of action, (2) enable the selection and combination of non-cross-resistant drugs, and (3) show where new drugs 'fit in' among established agents.
机译：一组六种“野生型”和三种VP-16抗药性小细胞肺癌（SCLC）细胞系用于评估使用克隆形成试验进行体外敏感性测试可在多大程度上有助于将细胞毒性药物联合用于治疗方案，从而提高抗SCLC。耐药株包括（a）H69 / DAU4，它是经典的多药耐药（MDR），带有P糖蛋白外排泵；（b）NYH / VM，它表现出拓扑异构酶II（topo II）活性改变；（c）H69 /对长春新碱有交叉耐药性的VP表现出与H69 / DAU4相似的减少的药物积累，但不含P-糖蛋白。小组中比较了19种抗癌药。如预期的那样，MDR品系对所有topo II药物具有交叉耐药性，但对BCNU，顺铂，ara-C，羟基脲和对topo I抑制剂喜树碱的侧支敏感性也有不同的模式。九种细胞系的完整面板清楚地展示了对具有不同作用方式的药物的多种敏感性模式。相关分析表明，类似药物之间（例如VP-16 / VM-26为0.99，长春新碱/长春地碱为0.89）以及具有相似作用机理的药物之间（例如BCNU /顺铂为0.89，VP-16 /阿霉素为0.92）具有较高的相关系数（CC）。 ），而不同的药物类别则显示出较低的CC甚至是阴性CC（例如BCNU / VP-16 -0.21）。当针对VP-16的19种药物模式的CC与针对BCNU的CC作图时，在作用于微管，topo II，烷基化剂和抗代谢物的药物之间观察到聚集。在该图中，喜树碱和ara-C模式因对烷基化剂和topo II药物缺乏交叉耐药性而很有希望。因此，该细胞组上不同的细胞毒性模式可以（1）提供有关药物作用机理的信息，（2）可以选择和组合非交叉耐药性药物，以及（3）显示新药物在哪里适合在已建立的代理商中。

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