Effect of GÖ6976 on Proliferation of Chronic Myeloid Leukemia Cells and Its Toxicity on Normal Cells and Mice.
10.19746/j.cnki.issn.1009-2137.2020.06.009
- Author:
Xiao-Peng CHEN
1
;
Zhen-Rui CAO
1
;
Min FENG
2
;
Yan LI
1
;
Jing HU
3
Author Information
1. First Clinical College of Chongqing Medical University; Chongqing 400016, China.
2. Basic Medical college of Chongqing Medical University; Chongqing 400016, China.
3. Laboratoirial Examination Medical Collage of Chongqing Medical University, Key Laboratory of Climical Labonatorial Diagnosis, Education Ministry, Chongqing 400016, China E-mail: jessie805@qq.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis;
Carbazoles;
Cell Proliferation;
Humans;
K562 Cells;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive;
Leukocytes, Mononuclear;
Mice;
Mice, Inbred BALB C
- From:
Journal of Experimental Hematology
2020;28(6):1842-1847
- CountryChina
- Language:Chinese
-
Abstract:
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.
