Sotomatsu M, Yugami S, Shitara T, Kuroume T
Department of Pediatrics, Gunma University School of Medicine, Maebashi, Japan.
Am J Hematol. 1993 Aug;43(4):251-5. doi: 10.1002/ajh.2830430404.
The effect of dipyridamole (DPM) on cell sensitivity to anticancer drugs was examined in acute lymphoblastic leukemia (ALL) cell lines. We established two ALL cell lines (KMO-90 and KMO-R) from bone marrow samples of a 12-year-old girl with ALL. The drug concentrations needed to reduce optical density to 50% of that of control cells (IC50) showed that KMO-R was about twofold more resistant to doxorubicin (DOX), mitoxantrone (MIT), vincristine (VCR), and etoposide (VP-16) than was KMO-90. Considering that both KMO-90 and KMO-R were established from a patient with ALL at the time of presentation and relapse, respectively, these two cell lines might be novel and useful models for research into the acquisition of drug resistance in ALL cells. Although cytotoxicity of DPM in KMO-90 was about 6% at 1 microgram/ml, DPM enhanced cell sensitivity to DOX, MIT, VCR, and VP-16 at this concentration. Cytotoxicity of DPM in KMO-R was less than 5% at 1, 5, and 10 micrograms/ml. In KMO-R, DPM enhanced cell sensitivity to these four drugs in a dose-dependent manner. The plasma concentrations achieved by oral administration of DPM is about 1 microgram/ml. At clinically achievable concentrations, DPM enhanced cell sensitivity to DOX, MIT, VCR, and VP-16 in both KMO-90 and KMO-R, thus showing DPM to be a useful agent for potentiating anticancer chemotherapy of hematopoietic malignancy.
在急性淋巴细胞白血病（ALL）细胞系中研究了双嘧达莫（DPM）对细胞对抗癌药物敏感性的影响。我们从一名12岁ALL女童的骨髓样本中建立了两个ALL细胞系（KMO - 90和KMO - R）。将光密度降低至对照细胞光密度50%所需的药物浓度（IC50）表明，KMO - R对阿霉素（DOX）、米托蒽醌（MIT）、长春新碱（VCR）和依托泊苷（VP - 16）的耐药性比KMO - 90高约两倍。鉴于KMO - 90和KMO - R分别是在初诊和复发时从一名ALL患者中建立的，这两个细胞系可能是研究ALL细胞耐药性获得的新型且有用的模型。尽管在1微克/毫升时DPM对KMO - 90的细胞毒性约为6%，但在此浓度下DPM增强了细胞对DOX、MIT、VCR和VP - 16的敏感性。在1、5和10微克/毫升时，DPM对KMO - R的细胞毒性小于5%。在KMO - R中，DPM以剂量依赖方式增强细胞对这四种药物的敏感性。口服DPM达到的血浆浓度约为1微克/毫升。在临床可达到的浓度下，DPM增强了KMO - 90和KMO - R细胞对DOX、MIT、VCR和VP - 16的敏感性，因此表明DPM是增强造血系统恶性肿瘤抗癌化疗效果的有用药物。
