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.
题目: Cyr61对慢性粒细胞白血病伊马替尼耐药的影响及其机制研究.
目的: 探讨Cyr61对慢性粒细胞白血病（CML）伊马替尼（IM）耐药的影响及相关机制.
方法: 采用酶联免疫吸附实验检测细胞培养上清中Cyr61含量，采用real-time PCR和Western blot检测细胞中Cyr61和Bcl-xL的表达水平，采用Annexin V-APC试剂盒分析细胞凋亡情况，通过Western blot检测细胞中信号通路相关蛋白的表达.
结果: 在CML IM耐药细胞系K562G细胞中Cyr61的表达水平增高。特异性下调Cyr61的表达降低了K562G细胞对IM的耐药性，促进IM诱导的细胞凋亡；在CML小鼠模型中，特异性下调Cyr61的表达能够提高K562G细胞对IM的敏感性。机制研究提示，Cyr61介导CML细胞IM耐药与Cyr61调控ERK1/2通路和凋亡相关分子Bcl-xL有关.
结论: Cyr61在促进CML细胞IM耐药中起着重要作用，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.
Keywords: Cyr61; chronic myeloid leukemia; drug resistance; imatinib.