Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Oncol Rep. 2013 Oct;30(4):1739-44. doi: 10.3892/or.2013.2654. Epub 2013 Aug 2.
Medulloblastoma (MB) is the most common malignant brain tumor in children and is highly invasive and metastatic. Despite recent advances, most MB patients suffer significant therapy-related morbidity, and the survival rate for patients with metastatic MB remains unsatisfactory. Altered expression of FOXM1 has been detected in many types of cancers, and the inhibition of FOXM1 has been studied as a cancer therapy. In the present study, we evaluated the impact of the inhibition of FOXM1 by thiostrepton in Daoy MB cells. Cells were treated with different concentrations of thiostrepton alone or in combination with cisplatin. Cell viability was measured with CCK-8 assays, and cell cycle distribution and apoptosis were assessed by flow cytometric analysis. Changes in protein expression were examined by western blotting. RNAi experiments were performed using siRNA oligonucleotides. The invasion and migration studies were performed using 8-µm Transwell plates. Inhibition of FOXM1 by thiostrepton significantly decreased MB cell proliferation. Cell arrest at the G2/M phase and apoptosis were significantly increased in MB cell lines that were treated with thiostrepton or transfected with siRNA. Thiostrepton decreased the IC50 value of cisplatin for MB treatment by enhancing cisplatin-induced apoptosis. Thiostrepton also decreased cell invasion and migration, which are crucial steps for tumor progression. Our data suggest that targeting FOXM1 with small-molecule inhibitors results in potent antitumor activity and chemosensitizing effects in human medulloblastoma cells.
髓母细胞瘤（MB）是儿童中最常见的恶性脑肿瘤，具有高度侵袭性和转移性。尽管最近取得了进展，但大多数 MB 患者仍遭受严重的治疗相关发病率，转移性 MB 患者的生存率仍不尽人意。FOXM1 的表达改变已在许多类型的癌症中被检测到，并且已经研究了抑制 FOXM1 作为癌症治疗的方法。在本研究中，我们评估了硫链丝菌素通过抑制 FOXM1 对 Daoy MB 细胞的影响。细胞分别用不同浓度的硫链丝菌素单独或与顺铂联合处理。用 CCK-8 法测量细胞活力，并通过流式细胞术分析评估细胞周期分布和细胞凋亡。通过 Western blot 检查蛋白表达的变化。使用 siRNA 寡核苷酸进行 RNAi 实验。使用 8-µm Transwell 板进行侵袭和迁移研究。硫链丝菌素抑制 FOXM1 显著降低 MB 细胞增殖。用硫链丝菌素处理或转染 siRNA 的 MB 细胞系中，G2/M 期细胞阻滞和凋亡明显增加。硫链丝菌素通过增强顺铂诱导的凋亡，降低了 MB 治疗中顺铂的 IC50 值。硫链丝菌素还降低了细胞侵袭和迁移，这是肿瘤进展的关键步骤。我们的数据表明，用小分子抑制剂靶向 FOXM1 可导致人髓母细胞瘤细胞产生强大的抗肿瘤活性和化疗增敏作用。
