Adenovirus-mediated delivery of bFGF small interfering RNA reduces STAT3 phosphorylation and induces the depolarization of mitochondria and apoptosis in glioma cells U251

Glioblastoma multiforme (gbm) carries a dismal prognosis primarily due to its aggressive proliferation in the brain regulated by complex molecular mechanisms. one promising molecular target in gbm is over-expressed basic fibroblast growth factor (bfgf),which has been correlated with growth,progression,and vascularity of human malignant gliomas. previously,we reported significant antitumor effects of an adenovirus-vector carrying bfgf small interfering rna (ad-bfgf-sirna) in glioma in vivo and in vitro. however,its mechanisms are unknown. signal transducer and activator of transcription 3 (stat3) is constitutively active in gbm and correlates positively with the glioma grades. in addition,as a specific transcription factor,stat3 serves as the convergent point of various signaling pathways activated by multiple growth factors and/or cytokines. therefore,we hypothesized that the proliferation inhibition and apoptosis induction by ad-bfgf-sirna may result from the interruption of stat3 phosphorylation. in the current study,we found that in glioma cells u251,ad-bfgf-sirna impedes the activation of erk1/2 and jak2,but not src,decreases il-6 secretion,reduces stat3 phosphorylation,decreases the levels of downstream molecules cyclind1 and bcl-xl,and ultimately results in the collapse of mitochondrial membrane potentials as well as the induction of mitochondrial-related apoptosis. our results offer a potential mechanism for using ad-bfgf-sirna as a gene therapy for glioma. to our knowledge,it is the first time that the bfgf knockdown using adenovirus-mediated delivery of bfgf sirna and its potential underlying mechanisms are reported. therefore,this finding may open new avenues for developing novel treatments against gbm. © 2011 liu et al; licensee biomed central ltd.