CXCR1 knockdown improves the sensitivity of osteosarcoma to cisplatin
CXCR1 knockdown improves the sensitivity of osteosarcoma to cisplatin
复制标题
CXCR1敲低提高骨肉瘤对顺铂的敏感性
DOI：
10.1016/j.canlet.2015.09.002
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发表时间：
2015-12-28
期刊：
影响因子：
9.7
通讯作者：
Tang, Ting-ting
中科院分区：
文献类型：
--
作者：
Han, Xiu-guo;Du, Lin;Tang, Ting-ting
化疗耐药是骨肉瘤患者预后不良的主要原因。本研究旨在确定CXCR 1基因敲低是否能提高骨肉瘤对化疗的敏感性。研究并比较了两种骨肉瘤细胞系中CXCR 1表达和顺铂敏感性。对化疗药物顺铂的敏感性和细胞凋亡进行了研究，有或没有刺激通过白细胞介素-8（IL-8），这是CXCR 1的配体。此外，确定Akt信号通路的活化。最后，将酶标记的CXCR 1敲低Saos 2肺细胞注射到裸鼠的胸腺中，此后用顺铂治疗。我们发现骨肉瘤细胞系中CXCR 1表达与顺铂敏感性呈负相关。IL-8诱导的敏感性降低可以通过沉默CXCR 1来阻断，并且OCCR 1敲低抑制Akt信号通路。此外，CXCR 1敲低的肿瘤显著小于对照肿瘤，这与荧光素酶强度结果一致。CXCR 1基因敲减细胞中IL-8、CXCR 1和p-Akt的表达水平受到抑制。综上所述，这些数据表明，CXCR 1基因敲低骨肉瘤细胞提高化疗的敏感性，这一过程可能部分由IL-8/CXCR 1/Akt信号通路调节。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Chemotherapy resistance is a major cause of poor prognoses for osteosarcoma patients. This study aimed to determine whether CXCR1 gene knockdown improves the sensitivity of osteosarcomas to chemotherapy. Both CXCR1 expression and cisplatin sensitivity were investigated and compared in two osteosarcoma cell lines. Sensitivity to the chemotherapy drug cisplatin and apoptosis were investigated with or without stimulation via Interleukin-8 (IL-8), which is a ligand of CXCR1. Furthermore, activation of the Akt signaling pathway was determined. Finally, luciferase-labeled CXCR1-knockdown Saos2-lung cells were injected into the tibiae of nude mice that were treated with cisplatin thereafter. We found that CXCR1 expression and cisplatin sensitivity were negatively correlated in osteosarcoma cell lines. IL-8-induced reduction in sensitivity could be blocked by silencing CXCR1, and OCCR1 knockdown suppressed the Akt signaling pathway. Moreover, CXCR1-knockdown tumors were significantly smaller than control tumors, which was consistent with the luciferase intensity results. The expression levels of IL-8, CXCR1 and p-Akt were suppressed in CXCR1-knockdown cells. Taken together, these data indicate that CXCR1 gene knockdown in osteosarcoma cells improved the sensitivity to chemotherapy and that this process might be regulated in part by the IL-8/CXCR1/Akt signaling pathway. (C) 2015 Elsevier Ireland Ltd. All rights reserved.