Dipyridamole enhancement of drug sensitivity in acute lymphoblastic leukemia cells.
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.
Department of Pediatrics, Gunma University School of Medicine, Maebashi, Japan.
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M
Sotomatsu
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S
Yugami
T
T
Shitara
T
T
Kuroume
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002648:Child; D004176:Dipyridamole / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004351:Drug Resistance; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D008942:Mitoxantrone / Q000008:administration & dosage / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014750:Vincristine; D004176:Dipyridamole; D005047:Etoposide; D004317:Doxorubicin; D008942:Mitoxantrone