Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Center of Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
CNS Neurosci Ther. 2020 Apr;26(4):475-485. doi: 10.1111/cns.13297.
Glioblastoma (GBM) is identified as a lethal malignant tumor derived from the nervous system. Despite the standard clinical strategy including maximum surgical resection, temozolomide (TMZ) chemotherapy, and radiotherapy, the median survival of GBM patients remains <15 months. Accumulating evidence indicates that rapid-acquired radioresistance is one of the most common reasons for GBM recurrence. Therefore, developing novel therapeutic targets for radioresistant GBM could yield long-term cures.
To investigate the functional role of CXCL1 in the acquired radioresistance and identify the molecular pathway correlated to CXCL1.
In this study, we identified that CXCL1 is highly expressed in GBM and the elevation of CXCL1 is involved in radioresistance and poor prognosis in GBM patients. Additionally, silencing CXCL1 attenuated the proliferation and radioresistance of GBM cells. Furthermore, we demonstrated that CXCL1-overexpression induced radioresistance through mesenchymal transition of GBM via the activation of nuclear factor-kappa B (NF-κB) signaling.
CXCL1 was highly enriched in GBM and positively correlated with poor prognosis in GBM patients. Additionally, elevated CXCL1 induced radioresistance in GBM through regulation of NF-κB signaling by promoting mesenchymal transition in GBM.
胶质母细胞瘤（GBM）是一种源自神经系统的致命恶性肿瘤。尽管包括最大限度手术切除、替莫唑胺（TMZ）化疗和放疗在内的标准临床策略被采用，但 GBM 患者的中位生存期仍<15 个月。越来越多的证据表明，快速获得性放射抵抗是 GBM 复发的最常见原因之一。因此，开发针对放射抵抗性 GBM 的新治疗靶点可能会带来长期治愈。
研究 CXCL1 在获得性放射抵抗中的功能作用，并确定与 CXCL1 相关的分子途径。
在这项研究中，我们发现 CXCL1 在 GBM 中高度表达，并且 CXCL1 的升高与 GBM 患者的放射抵抗和不良预后有关。此外，沉默 CXCL1 可减弱 GBM 细胞的增殖和放射抵抗能力。此外，我们还证明了 CXCL1 的过表达通过核因子-κB（NF-κB）信号通路的激活诱导 GBM 的间质转化，从而导致放射抵抗。
CXCL1 在 GBM 中高度富集，并与 GBM 患者的不良预后呈正相关。此外，升高的 CXCL1 通过促进 GBM 中的间质转化，调节 NF-κB 信号通路，诱导 GBM 的放射抵抗。
