Enhancement of sensitivity to adriamycin in resistant P388 leukemia by the calmodulin inhibitor trifluoperazine.
Enhancement of sensitivity to adriamycin in resistant P388 leukemia by the calmodulin inhibitor trifluoperazine.
复制标题
钙调蛋白抑制剂三氟拉嗪增强耐药 P388 白血病对阿霉素的敏感性。
作者：
Ram Ganapathi;D. Grabowski
已证明埃利希和P388小鼠肿瘤亚系对柔红霉素和阿霉素（ADR）的细胞毒性作用的抗性是由于药物的细胞蓄积和滞留减少。在这项研究中，钙调蛋白抑制剂三氟拉嗪的细胞积累，保留和细胞毒性作用的ADR在ADR敏感（P388/S）和ADR耐药（P388/R）P388小鼠白血病细胞的影响进行了测定。在悬浮培养24小时或1小时后接种在软琼脂中的细胞中，4 μ M三氟拉嗪的非细胞毒性浓度使P388/R细胞对ADR的敏感性提高2至6倍，但在P388/S细胞中则不然。三氟拉嗪处理后，ADR在P388/R细胞中的滞留比蓄积明显增强。这项研究表明吩噻嗪可能有新的用途，可以提高对ADR治疗耐药的肿瘤的药物敏感性。
Resistance to the cytotoxic effects of daunomycin and Adriamycin (ADR) in sublines of Ehrlich ascites and P388 mouse tumors has been demonstrated to be due to reduced cellular accumulation and retention of drug. In this study, the effect of the calmodulin inhibitor trifluoperazine on the cellular accumulation, retention, and cytotoxic effects of ADR in ADR-sensitive (P388/S) and ADR-resistant (P388/R) P388 mouse leukemia cells was determined. In cells treated in suspension culture for 24 hr or for 1 hr followed by plating in soft agar, a noncytotoxic concentration of 4 microM trifluoperazine, enhanced the sensitivity to ADR 2- to 6-fold in P388/R but not in P388/S cells. A marked enhancement in cellular retention rather than accumulation of ADR in only P388/R cells was obtained with trifluoperazine treatment. This study suggests the possible novel use of phenothiazines to improve drug sensitivity of tumors resistant to ADR treatment.
阿霉素敏感和阿霉素耐药 P388 小鼠白血病细胞的细胞内阿霉素水平和细胞毒性。
DOI：
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发表时间：
1982
期刊：
Journal of the National Cancer Institute
影响因子：
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作者：
Ganapathi,R;Reiter,W;Krishan,A
通讯作者：
Krishan,A