Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Adenovirus-mediated delivery of bFGF small interfering RNA reduces STAT3 phosphorylation and induces the depolarization of mitochondria and apoptosis in glioma cells U251 | Liu et al. Journal of Experimental Clinical Cancer Research 2011 30 80 http content 30 1 80 Journal of Experimental Clinical Cancer Research RESEARCH Open Access Adenovirus-mediated delivery of bFGF small interfering RNA reduces STAT3 phosphorylation and induces the depolarization of mitochondria and apoptosis in glioma cells U251 Jun Liu1 2 Xinnv Xu3 Xuequan Feng4 Biao Zhang5 and Jinhuan Wang 2 Abstract 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
