title: Soluble Flt-1 gene delivery in acute myeloid leukemic cells mediating a nonviral gene carrier.
abstract: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in angiogenesis-mediated progression of acute myeloid leukemia (AML). Studies have reported the role of soluble form of fms-like tyrosine kinase (sFlT-1) delivery as an antitumor agent by inhibiting VEGF. This study investigates the outcome of delivery of a VEGF165 antagonist, soluble vascular endothelial growth factor receptor, namely sFLT-1, mediating lipofectamine 2000 in acute myeloid leukemic cells. A recombinant plasmid expressing sFLT-1 was constructed and transfected into the K562 and HL60 cells using lipofectamine 2000 transfection reagent. sFLT-1 expression/secretion in pVAX-sFLT-1 transfected cells was verified by RT-PCR and western blot. MTS assay was carried out to evaluate the effect of sFLT-1 on human umbilical vein endothelial cells and K562 and HL60 cells in vitro. Treatment with pVAX-sFLT-1 showed no association between sFLT-1 and proliferation of infected K562 and HL60 cells, while it demonstrated a significant inhibitory impact on the proliferation of HUVECs. The results of the current study imply that the combination of nonviral gene carrier and sFLT-1 possesses the potential to provide efficient tool for the antiangiogenic gene therapy of AML.
authors.affiliation: Medical Genetics Laboratory, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Razieh
authors.initials: R
authors.lastname: Amini
authors.forename: Farid
authors.initials: F
authors.lastname: Azizi Jalilian
authors.forename: Abhi
authors.initials: A
authors.lastname: Veerakumarasivam
authors.forename: Syahril
authors.initials: S
authors.lastname: Abdullah
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Abdulamir
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Nadali
authors.forename: Rozita
authors.initials: R
authors.lastname: Rosli
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002465:Cell Movement; D049109:Cell Proliferation; D015973:Gene Expression Regulation, Leukemic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D018922:HL-60 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy; D008055:Lipids; D009389:Neovascularization, Pathologic; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; C086724:Lipofectamine; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1