Suppression of GLI sensitizes medulloblastoma cells to mitochondria-mediated apoptosis

作者：Zhongxiao Lin, Sisi Li, Hansong Sheng, Ming Cai, Lin Yuan, Liuxun Hu, Shangyu Xu, Li Yu, Nu Zhang · 发表于：Journal of Cancer Research and Clinical Oncology · 年份：2016 · DOI：10.1007/s00432-016-2241-1 · 被引用次数：31 · 研究领域：Hedgehog Signaling Pathway Studies、Pituitary Gland Disorders and Treatments、Congenital Ear and Nasal Anomalies

PURPOSE: The sonic hedgehog (SHH) signalling pathway plays the important role in medulloblastoma (MB). Altered GLI expression plays a key role in these processes, and the inhibition of GLI may be a good cancer-targeted therapy. This study aimed to investigate whether GANT61, a GLI inhibitor, may inhibit the SHH signalling pathway promoting cell mitochondria-mediated apoptosis and enhance cisplatin apoptosis antineoplastic therapy. METHODS: In our study, we determined the effect of GANT61-mediated inhibition of GLI in Daoy MB cells. Cells were treated with different concentrations of GANT61 alone or in combination with cisplatin. Cell proliferation was assessed with CCK-8 assays, and cell invasion and migration were performed using 8-µm transwell inserts. Cell apoptosis was assessed with flow cytometric analysis and rhodamine 123. qPCR was used to complete RNA experiments. Protein expression was assessed with Western blotting. RESULTS: The GANT61 significantly inhibited cell proliferation. GANT61 decreased the cell migration and invasion, impairing these crucial steps in tumour progression. Cell apoptosis was significantly increased in Daoy cells. Rhodamine 123 assay showed that GANT61 could decrease the mitochondrial membrane potential promoting cell mitochondria-mediated apoptosis. GANT61 inhibited the expression of GLI and Bcl-2 at both the mRNA and protein levels and might affect the expression of Bax, caspase-3 and caspase-9 to promote cell intrinsic apoptosis. Furthermor...