title: Combined effects of EGFR and Hedgehog signaling pathway inhibition on             the proliferation and apoptosis of pancreatic cancer cells.
abstract: In the present study, we established a new experimental model to investigate             the effects of EGFR targeting by RNAi, and the synergistic actions between the             hedgehog (Hh) and EGFR signaling pathways on the proliferation and apoptosis in             pancreatic cancer cells. Three human pancreatic cancer cell lines expressing EGFR             shRNA were established, and gene expression inhibition was assessed in these lines             using RT-PCR and western blot analysis. The effects of EGFR RNAi and Hh inhibition             on cell proliferation and apoptosis were explored in vitro and in vivo. We observed             that EGFR RNAi notably inhibited cell proliferation and colony formation, induced             apoptosis and markedly decreased xenograft tumor growth. Furthermore, EGFR RNAi             significantly enhanced cyclopamine sensitivity both in vitro and in vivo, and             a synergistic decrease of both AKT and ERK phosphorylation was observed. The present             study demonstrates that combined inhibition of both EGFR and Hh signaling pathways             could establish a more promising antitumor approach than inhibiting each singly,             and that there is a possible synergistic effect for Hh and EGFR signaling pathways             on ERK and AKT phosphorylation.
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, PR China.
authors.forename: Chang-Fu
authors.initials: CF
authors.lastname: Qin
authors.forename: Kun
authors.initials: K
authors.lastname: Hao
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Tian
authors.forename: Xue-Hai
authors.initials: XH
authors.lastname: Xie
authors.forename: Yin-Mo
authors.initials: YM
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D015398:Signal Transduction; D016019:Survival Analysis; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D053823:Hedgehog Proteins; D034741:RNA, Small Interfering; D066246:ErbB Receptors