Chloroquine enhancement of anticancer drug cytotoxicity in multiple drug resistant human leukemic cells.
Chloroquine enhancement of anticancer drug cytotoxicity in multiple drug resistant human leukemic cells.
复制标题
氯喹增强抗癌药物对多重耐药人白血病细胞的细胞毒性。
DOI：
10.1016/0006-2952(86)90710-0
复制
发表时间：
1986
影响因子：
5.8
通讯作者：
Beck,WT
中科院分区：
文献类型：
--
作者：
Zamora,JM;Beck,WT
用溶酶体剂氯喹处理长春花碱敏感（CCRF-CEM）和抗性（CEM/VLB100）人T细胞淋巴母细胞。通过生长抑制测量，该药物增强了长春花碱在 CEM/VLB100 细胞中的细胞毒性，但在 CCRF-CEM 细胞中效果较差。氯喹还增强了 CEM/VLB100 细胞中长春新碱、柔红霉素和多柔比星的细胞毒性活性，并在较小程度上增强了替尼泊苷 (VM-26) 的细胞毒性活性。组织学检查显示，长春花碱耐药细胞比药物敏感细胞含有更多的细胞质空泡。当 CEM/VLB100 细胞用氯喹、长春花碱或两者的组合处理时，细胞比对照组显示出更多的细胞质空泡。与液泡数量增加相一致，这些处理过的细胞对溶酶体酶、酸性磷酸酶的染色比对照细胞更强烈，但对脂质的染色则不然。当 CCRF-CEM 细胞系暴露于氯喹 + 长春碱组合时，空泡化没有增加那么多。空泡化也与长春新碱、阿霉素和柔红霉素治疗相关，但与 VM-26 无关。我们得出结论，氯喹是 CEM/VLB100 细胞系中抗癌药物作用的调节剂。
Vinblastine-sensitive (CCRF-CEM) and -resistant (CEM/VLB100) human T-cell lymphoblasts were treated with the lysosomotropic agent chloroquine. As measured by growth inhibition, this drug enhanced the cytotoxicity of vinblastine in the CEM/VLB100cells but was less effective in the CCRF-CEM cells. Chloroquine also enhanced the cytotoxic activity of vincristine, daunorubicin and doxorubicin and, to a lesser extent, teniposide (VM-26) in the CEM/VLB100cells. Histological examination revealed that the vinblastine-resistant cells contained more cytoplasmic vacuoles than their drug-sensitive counterparts. When the CEM/VLB100cells were treated with chloroquine, vinblastine, or a combination of the two, the cells displayed many more cytoplasmic vacuoles than the controls. Coincident with the increased number of vacuoles, these treated cells stained more intensely than controls for the lysosomal enzyme, acid phosphatase, but not for lipid. The vacuolization did not increase as much in the CCRF-CEM cell line when these cells were exposed to the chloroquine + vinblastine combination. Vacuolization was also associated with vincristine, doxorubicin, and daunorubicin treatments, but not with VM-26. We conclude that chloroquine is a modulator of anticancer drug action in the CEM/VLB100cell line.