Song Yan-Fang, Luo Li, Shi Peng-Chong, Li Zhao-Zhong, Zhang Tai-Gang, Cao Ying-Ping, Zhu Xian-Jin
Scientific Research Laboratory, Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350004, Fujian Province, China.
College of Integrated Chinese and Western Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou 350108, Fujian Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Feb;31(1):1-7. doi: 10.19746/j.cnki.issn.1009-2137.2023.01.001.
To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism.
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.
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.
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.
探讨Cyr61对慢性髓性白血病（CML）伊马替尼（IM）耐药的影响及其机制。
采用酶联免疫吸附测定法测定细胞培养上清液中Cyr61水平。通过实时PCR和蛋白质免疫印迹法检测Cyr61和Bcl-xL的表达。使用Annexin V-APC试剂盒分析细胞凋亡。通过蛋白质免疫印迹法测定信号通路相关蛋白的表达。
Cyr61水平在K562G细胞（对CML细胞系K562具有IM耐药性）中明显升高。下调Cyr61的表达降低了K562G细胞对IM的耐药性，并促进了IM诱导的细胞凋亡。在CML小鼠模型中，下调Cyr61的表达可增加K562G细胞对IM的敏感性。机制研究表明，Cyr61介导的CML细胞IM耐药性与Cyr61对ERK1/2通路和凋亡相关分子Bcl-xL的调节有关。
Cyr61在促进CML细胞对IM耐药中起重要作用。靶向Cyr61或其相关效应通路可能是克服CML细胞IM耐药的途径之一。
