title: Gene therapy of lung adenocarcinoma using herpes virus expressing a fusogenic membrane glycoprotein.
abstract: The aim of this study is to observe the in vitro-targeted destruction of lung adenocarcinoma using recombinant Type I herpes simplex virus (HSV-I)-mediated gibbon ape leukemia virus envelope glycoprotein (GALV.fus), controlled by UL38 promoter and cytomegalovirus promoter (CMVP). A recombinant HSV-I plasmid encoding the GALV.fus was transfected into green monkey kidney cells, the lung adenocarcinoma line A549, and the human fetal fibroblast cell line HFL-I GNHu5 in various doses. The effects and expression of in vitro GALV.fus were observed using an inverted microscope. Enhanced green fluorescence protein expression served as the contro1 for GALV.fus. Recombinant HSV-I virus was produced. Fusogenic recombinant virus infection led to cell fusions in A549 in a dose-dependent manner. Nonfusogenic viruses only produced conventional cytotoxic effects. Recombinant HSV-I with the CMVP initiated cell fusions in HFL-1 GNHu5 cells with arrested cell cycles or as quiescence. HSV-I regulated by UL38p caused cell fusion only in growing cells. Protein expression of GALV.fus was confirmed by Western Blot in infected A549 and HFL-1 GNHu5. Delivery and tumor-specific expression of GALV.fus gene can selectively and safely target lung cancer in vitro, and may prove to be a novel gene therapy for lung cancer.
authors: Department of Cardiothoracic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China, drzhubing@tom.com.
authors: Bing
authors: B
authors: Zhu
authors: Jian-ru
authors: JR
authors: Yang
authors: Yue-quan
authors: YQ
authors: Jiang
authors: Shi-feng
authors: SF
authors: Chen
authors: Xin-ping
authors: XP
authors: Fu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004274:DNA, Recombinant / Q000235:genetics; D015870:Gene Expression; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017989:Leukemia Virus, Gibbon Ape / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D010957:Plasmids / Q000235:genetics; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics*
chemical_list: D004274:DNA, Recombinant; D014760:Viral Fusion Proteins