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Adenovirus vector-mediated Gli1 siRNA induces growth inhibition and apoptosis in human pancreatic cancer with Smo-dependent or Smo-independent Hh pathway activation in vitro and in vivo

التفاصيل البيبلوغرافية
العنوان: Adenovirus vector-mediated Gli1 siRNA induces growth inhibition and apoptosis in human pancreatic cancer with Smo-dependent or Smo-independent Hh pathway activation in vitro and in vivo
المؤلفون: Xiao-hua Man, Hongyu Wu, Jing Jin, Zhao-Shen Li, Yan-fang Gong, Jiefang Guo, Jun Gao
المصدر: Cancer Letters. 339:185-194
بيانات النشر: Elsevier BV, 2013.
سنة النشر: 2013
مصطلحات موضوعية: Patched Receptors, Cancer Research, Genetic Vectors, Gene Expression, Apoptosis, Receptors, Cell Surface, Biology, Zinc Finger Protein GLI1, Adenoviridae, Receptors, G-Protein-Coupled, Mice, chemistry.chemical_compound, Cyclin D2, In vivo, Cell Line, Tumor, Animals, Humans, Hedgehog Proteins, RNA, Small Interfering, Cell Proliferation, Oncogene Proteins, Cell growth, Cell Cycle Checkpoints, Smoothened Receptor, Xenograft Model Antitumor Assays, Hedgehog signaling pathway, Tumor Burden, Pancreatic Neoplasms, Patched-1 Receptor, Disease Models, Animal, Proto-Oncogene Proteins c-bcl-2, Oncology, chemistry, Cell culture, Trans-Activators, Cancer research, Growth inhibition, Signal transduction, Signal Transduction
الوصف: Activation of Hedgehog (Hh) signaling pathway is a core molecular mechanism in pancreatic carcinogenesis. However, the inhibition of upstream Hh signals does not inhibit the growth of a subset of pancreatic cancer (PC). This study was to examine the effect of siRNA targeting Gli1, the downstream component of Hh pathway, on PC cells and to provide some insight into the underlying mechanisms. A Gli1siRNA-expressing adenovirus (Ad-U6-Gli1siRNA) was constructed, and its effect on PC cells was investigated in vitro and in vivo. Gli1 was expressed in 83.3% (20/24) PC tissues, whereas no expression was found in normal pancreatic ductal epithelium. Gli1 was expressed in SW1990 and CFPAC cells in which Smo was completely absent, as well as in PaTu8988, Panc-1 and BxPC-3 cells in which Smo was concomitantly present. Ad-U6-Gli1siRNA induced cell growth inhibition, strong G0/G1 cell cycle arrest and apoptosis in all five human PC cell lines. Meanwhile, Ad-U6-Gli1siRNA significantly suppressed the expression of Gli1, Ptch1 and two target genes, Cyclin D2 and Bcl-2, in all five lines. Furthermore, two tumor xenograft nude mice models were established by subcutaneously injecting Smo-positive Panc-1 cells or Smo-negative SW1990 cells. The in vivo experimental results demonstrated that Ad-U6-Gli1siRNA inhibited the growth of both Panc1-derived and SW1990-derived tumors and induced cell apoptosis. Our study indicates that Gli1-targeting siRNA could induce growth inhibition and apoptosis in PC through knockdown of Gli1 and its target genes; and this method may represent a more effective therapeutic strategy for PC with Smo-dependent or Smo-independent Hh pathway activation.
تدمد: 0304-3835
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1dfe0b84241bc0bbe332dbe3642b0ff4
https://doi.org/10.1016/j.canlet.2013.06.010
رقم الأكسشن: edsair.doi.dedup.....1dfe0b84241bc0bbe332dbe3642b0ff4
قاعدة البيانات: OpenAIRE
الوصف
تدمد:03043835