Combination of simvastatin and imatinib sensitizes the CD34+ cells in K562 to cell death.
Chronic myeloid leukemia (CML) is a hematological malignancy, 95% of which is due to translocation between chromosomes 9 and 22 and the resulting bcr-abl fusion protein. Imatinib specifically binds to the bcr-abl and inhibits cancer cells. However, a subpopulation of the CML cells named leukemia stem cells are resistant to the imatinib therapy, leading to the relapse. In this study, we identified a subpopulation of CD34+ cells in K562 were much more resistant to imatinib than the bulk cells. Simvastatin single also had little pro-apoptotic effect on the CD34+ cells. In contrast, combination of simvastatin and imatinib induced a significant cell death in the subpopulation, which is dependent on the induced ROS by simvastatin as the effect was blocked by ROS scavenger N-acetyl-L: -cysteine (NAC). Our data here point out that combination of simvastatin and imatinib could be a therapeutic option for the resistant CML.
Chen
Rui
R
Department of Blood Transfusion, Xijing Hospital, The Fourth Military Medical University, 710032, Xi'an, China.
Xiao
Wei
W
Li
Ding
D
Mu
Shijie
S
D018952:Antigens, CD34 / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001549:Benzamides; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002469:Cell Separation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D017382:Reactive Oxygen Species; D019821:Simvastatin / Q000008:administration & dosage*
D018952:Antigens, CD34; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D000068877:Imatinib Mesylate; D019821:Simvastatin