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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis*
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Blotting, Western
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology*
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Cell Proliferation
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Fibroblast Growth Factor 2 / antagonists & inhibitors*
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Fibroblast Growth Factor 2 / genetics
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Fibroblast Growth Factor 2 / metabolism
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Flow Cytometry
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Glioblastoma / genetics
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Glioblastoma / metabolism
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Glioblastoma / pathology*
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Humans
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Membrane Potential, Mitochondrial
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics*
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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STAT3 Transcription Factor / antagonists & inhibitors*
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism
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Signal Transduction*
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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RNA, Messenger
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RNA, Small Interfering
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STAT3 Transcription Factor
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Fibroblast Growth Factor 2
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Phosphatidylinositol 3-Kinases