Anticancer effects of FL34 through the inhibition of GLI1 in glioblastoma

• DOI: 10.4103/jcrt.jcrt_564_18
• Publication Date: 2019-08-12T13:26:33Z
• Authors: Yan Li; Xueji Li; Ke Tang; Lulu Huang; Chunxia Liu; Qianqian Du; Tiegang Li; Chen Yan; Zhiqiang Feng
• Keywords: GLI1; Smoothened

The hedgehog (HH) signaling pathway is abnormally activated in glioblastoma (GBM); thus, its downstream effector GLI1 may be a suitable target for the treatment of GBM. aim present study was to evaluate antitumor activities novel compound, FL34, GBM through inhibition GLI1.The effect FL34 on suppressing proliferation, angiogenesis, and invasion cells investigated vitro using invasion, tube formation, flow cytometry, dual luciferase, reverse transcription-quantitative polymerase chain reaction, western blot assays. A subcutaneously transplanted orthotopic U-87 MG cell xenograft model used tumor growth vivo.The results demonstrated that markedly inhibited angiogenesis GBM, addition decreasing transcriptional activity expression GLI1, resulting downregulation genes, including B-cell lymphoma-2, vascular endothelial factor, matrix metalloproteinases. Furthermore, activation without influencing upstream canonical HH/Smoothened or crosstalk with other oncogenic pathways, Ras/ERK AKT signaling. At dose 30.0 mg/kg, suppressed by 78.74% weight models 64.24% volume models.These data suggested exerted mediated potential candidate compound could develop new drugs