title: A novel multi-target RNAi adenovirus inhibits hepatoma cell proliferation, migration, and induction of angiogenesis.
abstract: The pathogenesis of hepatocellular carcinoma (HCC) is a multi-step process involving many genes. Consequently, single gene targeting therapy has limited efficacy, making combination therapy targeting multiple genes a necessity. Based on our previous findings, we constructed a single vector mediating simultaneous expression of multiple short hairpin RNAs (shRNAs) against human vascular endothelial growth factor receptor 2 (VEGFR2), chemokine C-C motif receptor 1 (CCR1), and epithelial cell adhesion molecule (EpCAM), three genes closely related to HCC progression that act through separate pathways. The shRNA vector efficiently downregulated the mRNA and protein of all three molecules in Huh7 hepatoma cells. The vector also inhibited cell proliferation and migration and reduced angiogenesis. Furthermore, this shRNA vector can be recombined into adenovirus, a gene therapy vector, for better in vivo application. It thus offers a potentially effective future gene therapy approach to treating human liver cancer.
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Huang
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China.
authors.forename: Guangyao
authors.initials: G
authors.lastname: Li
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Pan
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Ren
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China.|Department of Hepatic Surgery, Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Jia
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China.|Department of Hepatic Surgery, Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Ma
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China.|Department of Hepatic Surgery, Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001, China.
authors.forename: Geliang
authors.initials: G
authors.lastname: Xu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism; D005434:Flow Cytometry; D015316:Genetic Therapy; D005822:Genetic Vectors; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000628:therapy; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009389:Neovascularization, Pathologic; D034622:RNA Interference; D054389:Receptors, CCR1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: C515300:CCR1 protein, human; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D054389:Receptors, CCR1; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: CCR1; EpCAM; VEGFR2; adenovirus; hepatocellular carcinoma