Blocking the bFGF/STAT3 interaction through specific signaling pathways induces apoptosis in glioblastoma cells

Jingchao Wu; Xuequan Feng; Biao Zhang; Jialin Li; Xinnv Xu; Jun Liu; Xiuyu Wang; Jinhuan Wang; Xiaoguang Tong

doi:10.1007/s11060-014-1529-8

Blocking the bFGF/STAT3 interaction through specific signaling pathways induces apoptosis in glioblastoma cells

J Neurooncol. 2014 Oct;120(1):33-41. doi: 10.1007/s11060-014-1529-8. Epub 2014 Jul 22.

Authors

Jingchao Wu¹, Xuequan Feng, Biao Zhang, Jialin Li, Xinnv Xu, Jun Liu, Xiuyu Wang, Jinhuan Wang, Xiaoguang Tong

Affiliation

¹ Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, 300060, People's Republic of China.

PMID: 25048528
DOI: 10.1007/s11060-014-1529-8

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

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis*
Blotting, Western
Brain Neoplasms / genetics
Brain Neoplasms / metabolism
Brain Neoplasms / pathology*
Cell Proliferation
Fibroblast Growth Factor 2 / antagonists & inhibitors*
Fibroblast Growth Factor 2 / genetics
Fibroblast Growth Factor 2 / metabolism
Flow Cytometry
Glioblastoma / genetics
Glioblastoma / metabolism
Glioblastoma / pathology*
Humans
Membrane Potential, Mitochondrial
Mice
Mice, Inbred BALB C
Mice, Nude
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
RNA, Messenger / genetics
RNA, Small Interfering / genetics*
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
STAT3 Transcription Factor / antagonists & inhibitors*
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism
Signal Transduction*
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

RNA, Messenger
RNA, Small Interfering
STAT3 Transcription Factor
Fibroblast Growth Factor 2
Phosphatidylinositol 3-Kinases