Effect of Cyr61 on Imatinib Resistance in Chronic Myeloid Leukemia and Its Mechanism.
10.19746/j.cnki.issn.1009-2137.2023.01.001
- Author:
Yan-Fang SONG
1
;
Li LUO
2
;
Peng-Chong SHI
3
;
Zhao-Zhong LI
3
;
Tai-Gang ZHANG
2
;
Ying-Ping CAO
3
;
Xian-Jin ZHU
4
Author Information
1. Scientific Research Laboratory, Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350004, Fujian Province, China.
2. College of Integrated Chinese and Western Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou 350108, Fujian Province, China.
3. Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, China.
4. Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, China,E-mail: zxj5027667@163.com.
- Publication Type:Journal Article
- Keywords:
Cyr61;
chronic myeloid leukemia;
drug resistance;
imatinib
- MeSH:
Animals;
Humans;
Mice;
Apoptosis;
Drug Resistance, Neoplasm;
Imatinib Mesylate/pharmacology*;
K562 Cells;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism*;
Signal Transduction
- From:
Journal of Experimental Hematology
2023;31(1):1-7
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism.
METHODS:Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot.
RESULTS:The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61.
CONCLUSION:Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.