title: Effect of small interfering RNA targeting wild-type FLT3 in acute myeloid leukaemia cells in vitro and in vivo.
abstract: This study investigated the effect of using small interfering RNA (siRNA) to silence the wild-type FMS-like tyrosine kinase 3 (FLT3) gene in acute myeloid leukaemia (AML) cells, in vitro and in vivo. FLT3 siRNA was introduced into the human AML cell line, THP1,  and into a THP1 xenograft tumour model in BALB/c nude mice. FLT3 siRNA effectively reduced both the mRNA and the protein levels of FLT3, arrested cells in G(0)/G(1) phase, inhibited THP1 cell proliferation and increased apoptosis. Intraperitoneal injection of FLT3 siRNA suppressed  tumour growth in BALB/c nude mice. FLT3 siRNA treatment also reduced cyclin D1 and Bcl-2 protein levels, and increased the nuclear level of silencing mediator for retinoic acid and thyroid hormone receptors protein both in vitro and in vivo. These data suggest that FLT3 siRNA  is a strong inhibitor of FLT3 expression in vitro and in vivo, and may provide a new therapeutic target for AML.
authors: Department of Paediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
authors: C-M
authors: CM
authors: Wang
authors: G-Y
authors: GY
authors: Sheng
authors: J
authors: J
authors: Lu
authors: L
authors: L
authors: Xie
authors: S-T
authors: ST
authors: Bai
authors: X-J
authors: XJ
authors: Xu
authors: Y-F
authors: YF
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D056985:Nuclear Receptor Co-Repressor 2 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D047368:Tumor Burden; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D019938:Cyclin D1; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3