RESUMO
OBJECTIVE@#To investigate the effect of GÖ6976 on the proliferation of chronic myeloid leukemia cells and its toxic effect on normal cells and mice, so as to provide experimental basis for the effectiveness and safety of its clinical application.@*METHODS@#Different concentrations of GÖ6976 were applied to the K562 cells, human peripheral blood mononuclear cells (PBMNC) and normal BaF3 cells, MTT assay was used to detect the effect on cell proliferation. BALB/C mice were used to investigate the toxicity in vivo. The general situation, body weight and the number of white blood cells in peripheral blood were monitored during administration, the blood collected from eyeballs before and after administration was used for biochemical examination, at the same time, the liver, kidney and femurs were examined pathologically.@*RESULTS@#GÖ6976 could significantly inhibit the proliferation of K562 cells, inhibition effect increased with increasing dose (r=0.9623). However, there was no significant change in the inhibitory effect on PBMNC and BaF3 cells. The pathological examination of organs in each group showed no abnormal manifestations such as inflammatory infiltration, while the change rate of leukocyte count in peripheral blood of high dose group fluctuated greatly (P＜0.05), which might be related to the inhibition of intracellular protein kinase C, and no abnormality was observed in blood biochemical indexes. In the low dose group, there was no significant difference in peripheral blood leukocyte count, blood biochemical index and histopathology during administration drug as compared with the control group.@*CONCLUSION@#GÖ6976 possesses a significant inhibitory effect on the proliferation of K562 cells, and the inhibitory effect increases with increasing dose. Long-term application of 5.0 μmol/L and below concentrations of GÖ6976 shows no obvious inhibitory effect on PBMNC, BaF3 cells. Long-term application of 10 mg/kg and below concentrations of GÖ6976 shows no obvious toxic effect on BALB/c mice.
Assuntos
Animais , Humanos , Camundongos , Apoptose , Carbazóis , Proliferação de Células , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucócitos Mononucleares , Camundongos Endogâmicos BALB CRESUMO
Abstract Chronic myelogenous leukemia (CML) is a hematological malignancy that seriously threatens the lives of patients. It was found that there are abnormal classic Wnt pathway, that is, Wnt/β-catenin signaling pathways in CML cells, moreover, Wnt/β-catenin signaling pathway is involved in the growth and proliferation of CML cells, and closely relates with the self-renewal ability of CML leukemic stem cells. This review summarizes the recent studies on the relationship between Wnt/β-catenin signaling pathway and CML, and the researches on the targeting inhibition of Wnt/β-catenin signaling pathway in CML treatment, thus to provide new ideas for the treatment of CML.
RESUMO
Abstract At present, allogeneic hematopoietic stem cell transplantation is still the only way to cure chronic myelogenous leukemia. With the advances of HLA matching technology, application of tyrosine kinase inhibitors before and after transplantation, improvement of postoperative immune status and fusion gene monitoring, and the control of postoperative complications, especially graft-versus-host disease etc. allogeneic hematopoietic stem cell transplantation is displaying better efficacy in the treatment of chronic myelogenous leukemia, and the quality of life of patients has also been significantly improved. This article reviews the recent research advances on the allogeneic hematopoietic stem cell transplantation and related support technologies for treatment of chronic myeloid leukemia.