EF defined the experimental plan and executed with JL’s help. FT and EF drafted the manuscript and finalized it. All authors read and approved the final manuscript”
“1. Introduction Glioblastoma P505-15 cost multiforme (GBM) is the most common primary

malignant brain tumor in adults. Despite technological advances in surgical resection followed by the application of combined radiotherapy and chemotherapy, GBM patients have a median overall survival of nearly one year [1, 2]. A wide variety of genetic alterations that are frequently found in GBM are known to promote the malignant phenotype, including the abnormal activation of the PI3K-AKT and Ras-Raf-MEK-MAPK signaling pathways, the suppression of p53, retinoblastoma protein, and PTEN,

as well as the amplification and/or alteration of epidermal growth factor receptor (EGFR) and vascular endothelial GF120918 molecular weight growth factor receptor (VEGFR) [3–5]. Basic fibroblast growth factor (bFGF), a heparin-binding polypeptide growth factor, exerts mitogenic and angiogenic effects on human astrocytic tumors in an autocrine way [6]. Overexpression of bFGF, but not of fibroblast growth factor receptor1, in the nucleus correlates with the poor prognosis of gliomas [7]. Thus, bFGF may be a promising target for novel therapeutic approaches in glioma. Previously, we reported that adenovirus-mediated delivery of bFGF small interfering RNA (Ad-bFGF-siRNA) selleck chemicals showed antitumor effects and enhanced the sensitivity of glioblastoma cells to chemotherapy in glioma cell U251 [8, 9]. However, the major mechanisms involved remain unknown. Recently, the signal transducer and activator of transcription3 (STAT3) signaling pathway, which is constitutively selleck products activated in a variety of human neoplasms [10], such as leukemia, head and neck

cancer, melanoma, breast cancer, prostate cancer, and glioma, has become a focal point of cancer research. In GBM, abnormally activated STAT3 activates a number of downstream genes to regulate multiple behaviors of tumor cells, such as survival, growth, angiogenesis, invasion, and evasion of immune surveillance. This aberrant STAT3 activation correlates with the tumor grades and clinical outcomes [11]. STAT3 can be activated by IL-6-family cytokines in the classic IL-6/JAK pathway [12, 13] and by the growth factors EGF, FGF, and platelet-derived growth factor (PDGF) in target cells expressing receptor tyrosine kinases [14]. The oncoprotein Src can also directly activate STAT3 [15]. Given the fact that bFGF can activate the STAT3 pathway in many cell types, we investigated in this study whether the antitumor effects of Ad-bFGF-siRNA correlate with the reduced activation of the STAT3 signaling pathway to further our current understanding of the underlying mechanisms of Ad-bFGF-siRNA-induced growth suppression and apoptosis of glioma cells. 2. Materials and methods 2.