title: Blocking the bFGF/STAT3 interaction through specific signaling pathways induces apoptosis in glioblastoma cells.
abstract: We have reported that basic fibroblast growth factor (bFGF) demonstrates an intimate connection with signal transducer and activator of transcription 3 (STAT3) in malignant brain tumor cells. However, its mechanisms are still unclear. In this study, we used inhibitors to block specific signaling pathways, including JAK, PI3K/Akt, and Src pathways, to explore how bFGF mediates crosstalk with STAT3 in two glioblastoma(GBM) cell lines: U251 (mutant p53) and U87 (wild-type p53). Furthermore, we explored how the bFGF/STAT3 pathway affects GBM cell apoptosis. Our results suggest that bFGF can induce the activation of STAT3 mainly through the JAK and PI3K/Akt pathways, and that siRNA-mediated knockdown of STAT3 markedly reduces the bFGF levels in U251 cells. Our results also suggest that STAT3 knockdown increases the expression of pro-apoptotic genes and decreases the expression of anti-apoptotic genes, subsequently collapsing the mitochondrial membrane potentials in vitro and impairs tumor growth in vivo.
authors.affiliation: Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, 300060, People's Republic of China.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Wu
authors.forename: Xuequan
authors.initials: X
authors.lastname: Feng
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
authors.forename: Jialin
authors.initials: J
authors.lastname: Li
authors.forename: Xinnv
authors.initials: X
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Wang
authors.forename: Jinhuan
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Tong
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases