DOXORUBICIN SENSITIVITY PATTERN IN A PANEL OF SMALL-CELL LUNG-CANCER CELL-LINES - CORRELATION TO ETOPOSIDE AND VINCRISTINE SENSITIVITY AND INVERSE CORRELATION TO CARMUSTINE SENSITIVITY
DOXORUBICIN SENSITIVITY PATTERN IN A PANEL OF SMALL-CELL LUNG-CANCER CELL-LINES - CORRELATION TO ETOPOSIDE AND VINCRISTINE SENSITIVITY AND INVERSE CORRELATION TO CARMUSTINE SENSITIVITY
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DOI：
10.1007/bf00695993
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发表时间：
1992-10-01
影响因子：
3
通讯作者：
HANSEN, HH
中科院分区：
文献类型：
--
作者：
JENSEN, PB;ROED, H;HANSEN, HH
我们研究的目的是评估小细胞肺癌（SCLC）细胞系的体外敏感性模式是否可用于评估新药和选择药物以优化联合治疗。在我们试图获得一组表现出敏感性差异模式的细胞系时，我们开发了三种表现出不同类型的多药耐药性 (MDR) 的 SCLC 细胞系。在本研究中，我们比较了 5 个野生型 SCLC 细胞系和 3 个 MDR 细胞系对六种不同类型药物（阿霉素、阿糖胞苷、卡莫司汀）的敏感性模式。顺铂、长春新碱和依托泊苷。在野生型 SCLC 细胞系中，对所有药物的敏感性变化范围在 10 倍以内。对阿霉素表现出低敏感性的细胞系对依托泊苷和长春新碱也表现出低敏感性，反之亦然。相比之下。对卡莫司汀的敏感性模式几乎与阿霉素相反。当近静止细胞和暴露于代谢抑制剂 2-脱氧-D-葡萄糖的细胞中阿霉素敏感性降低时，也观察到阿霉素和卡莫司汀敏感性之间呈反比关系的趋势。与野生型品系观察到的模式一致，所有 MDR 亚品系均表现出对卡莫司汀的附带敏感性。至于阿糖胞苷，野生型株系表现出与阿霉素响应相似的敏感性模式。有趣的是，在 MDR 细胞系中发现了相反的模式，因为所有三个细胞都表现出阿糖胞苷过敏。烷化剂和“MDR”药物的组合在治疗实体瘤方面已被证明具有临床益处，蒽环类药物和阿糖胞苷的组合在急性髓系白血病中也是如此。因此，阿糖胞苷、烷化剂和 MDR 药物（即依托泊苷、阿霉素、长春新碱）的实验得出的敏感性数据与这些药物的临床经验相似，我们得出的结论是，对所述 SCLC 细胞系组使用克隆形成测定可以为选择联合治疗药物提供有价值的信息。
The aim of our investigations is to evaluate whether the sensitivity patterns of small-cell lung-cancer (SCLC) cell lines in vitro can be used in evaluating new drugs and in selecting drugs for the optimization of combination therapy. In our attempts to obtain a panel of cell lines demonstrating differential patterns in sensitivity, we have developed three SCLC lines exhibiting different types of multidrug resistance (MDR). In the present investigations we compared the sensitivity patterns shown by five wild-type SCLC lines and three MDR lines in response to six different types of drugs: doxorubicin, cytarabine, carmustine. cisplatin, vincristine, and etoposide. In the wild-type SCLC cell lines, the range of variation in sensitivity to all drugs was within a factor of 10. Cell lines showing low sensitivity to doxorubicin also exhibited low sensitivity to etoposide and vincristine, and vice versa. In contrast. the pattern of sensitivity to carmustine was almost the opposite of that to doxorubicin. A tendency to an inverse relationship between doxorubicin and carmustine sensitivity was also observed when doxorubicin sensitivity was reduced in near stationary cells and in cells exposed to the metabolic inhibitor 2-deoxy-D-glucose. In agreement with the pattern observed for the wild-type lines, all of the MDR sublines demonstrated collateral sensitivity to carmustine. As to cytarabine, the wild-type lines expressed a sensitivity pattern similar to that shown in response to doxorubicin. Interestingly, the opposite pattern was found in the MDR lines, as all three demonstrated cytarabine hypersensitivity. The combination of alkylating agents and "MDR" drugs are of proven clinical benefit in the treatment of solid tumors, as is the combination of anthracycline and cytarabine in acute myeloid leukemia. The experimentally derived sensitivity data on cytarabine, alkylating agents, and MDR drugs (i.e., etoposide, doxorubicin, vincristine) thus resemble the clinical experience with these drugs, and we conclude that the use of a clonogenic assay on the described panel of SCLC cell lines can give valuable information for the selection of agents for combination therapy.