Cyr61 decreases Cytarabine chemosensitivity in acute lymphoblastic leukemia cells via NF-B pathway activation
Cyr61 decreases Cytarabine chemosensitivity in acute lymphoblastic leukemia cells via NF-B pathway activation
复制标题
Cyr61 通过激活 NF-κB 通路降低急性淋巴细胞白血病细胞的阿糖胞苷化疗敏感性
DOI：
10.3892/ijmm.2018.4018
复制
发表时间：
2019-02-01
影响因子：
5.4
通讯作者：
Hu, Jianda
中科院分区：
文献类型：
--
作者：
Cao, Yingping;Wu, Conglian;Hu, Jianda
据报道，在各种恶性肿瘤中，Cyr61水平升高。Cyr61蛋白水平的升高与肿瘤细胞的增殖、转移和化疗耐药有关。此前，研究发现急性淋巴细胞白血病(ALL)患者血浆和骨髓上清液中的Cyr61均升高，促进ALL细胞存活。然而，Cyr61在ALL细胞化疗耐药中的作用尚不清楚。本研究的目的是研究Cyr61在调节所有细胞对Ara-C的化疗敏感性中的作用。研究发现，在ALL患者的骨髓单个核细胞中，Cyr61过表达。升高的Cyr61能有效减少Ara-C诱导的ALL细胞的凋亡，其作用可被抗Cyr61单抗093G9阻断。此外，Cyr61可上调Ara-C处理的ALL细胞中Bcl2的表达水平。从机制上讲，Cyr61部分地通过核因子-B途径影响所有细胞对Ara-C的抗性。综上所述，据我们所知，本研究是第一次揭示Cyr61通过核因子-B途径参与所有细胞耐药。这一发现支持了Cyr61在促进化疗耐药中的功能作用，提示直接靶向Cyr61或其相关的效应通路可能会改善ALL患者的临床反应。
Elevated Cyr61 levels have been reported in various malignancies. Elevation of Cyr61 protein levels contributes to the proliferation, metastasis, and chemotherapy resistance of malignant cells. Previously, it was discovered that Cyr61 is elevated in both the plasma and the bone marrow supernatants of patients with acute lymphoblastic leukemia (ALL), promoting ALL cell survival. However, the role of Cyr61 in the chemotherapeutic resistance of ALL cells remains unknown. The aim of the current study was to investigate the role of Cyr61 in regulating ALL cell chemosensitivity to Ara-C. It was found that Cyr61 is overexpressed in bone marrow mononuclear cells from patients with ALL. Increased Cyr61 effectively decreased Ara-C-induced apoptosis of ALL cells, and its function was blocked by the use of the anti-Cyr61 monoclonal antibody 093G9. Furthermore, Cyr61 increased the level of Bcl-2 in Ara-C-treated ALL cells. Mechanistically, it was shown that Cyr61 affected ALL cell resistance to Ara-C partially via the NF-B pathway. Taken together, the present study is the first, to the best of our knowledge, to reveal that Cyr61 is involved in ALL cell resistance through the NF-B pathway. The findings support a functional role for Cyr61 in promoting chemotherapy resistance, suggesting that targeting Cyr61 directly or its relevant effector pathways may improve the clinical responses of patients with ALL.