Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Gulou District, Nanjing, 210029, People's Republic of China.
Department of Neurosurgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China.
Pathol Oncol Res. 2020 Oct;26(4):2597-2604. doi: 10.1007/s12253-020-00827-x. Epub 2020 Jul 6.
Glioblastoma (GBM) are life-threatening tumors with a poor prognosis and low cure rates. GBMs are malignant brain tumors that develop from astrocytes. Most GBMs are not inherited and occur sporadically. GBM recurrence after standard treatment has led to the assessment of agents targeting the CXCR4 chemokine receptor as alternative drug target for much needed GBM therapeutics. In present study, a novel CXCR4 inhibitor modified with a picolinamide scaffold (CPZ1344) was designed and synthesized. Its anti-GBM function was then evaluated. Our results showed that CPZ1344 reduced the growth of GBM cells in a concentration dependent manner. The anti-GBM activity of CPZ1344 was due to alteration in GBM-cell morphology and apoptotic induction in GBM cells. CPZ1344 inhibited the migration and angiogenesis of U87 cells, led to cell cycle arrest in the G1 phase and inhibited CXCR4 signaling. These findings demonstrate the anticancer effects of CPZ1344 and its potential as a novel anti-GBM therapeutic.
胶质母细胞瘤（GBM）是具有预后不良和低治愈率的危及生命的肿瘤。GBM 是源自星形胶质细胞的恶性脑肿瘤。大多数 GBM 不是遗传性的，而是偶发性的。标准治疗后 GBM 的复发导致了针对 CXCR4 趋化因子受体的药物评估，作为急需的 GBM 治疗的替代药物靶点。在本研究中，设计并合成了一种用吡啶甲酰胺支架修饰的新型 CXCR4 抑制剂（CPZ1344）。然后评估了其抗 GBM 功能。我们的结果表明，CPZ1344 以浓度依赖的方式降低 GBM 细胞的生长。CPZ1344 的抗 GBM 活性是由于 GBM 细胞形态的改变和 GBM 细胞的凋亡诱导。CPZ1344 抑制 U87 细胞的迁移和血管生成，导致细胞周期停滞在 G1 期，并抑制 CXCR4 信号。这些发现表明 CPZ1344 具有抗癌作用，可能是一种新型的抗 GBM 治疗药物。
