title: Gene delivery of apoptin-derived peptide using an adeno-associated virus vector inhibits glioma and prolongs animal survival.
abstract: Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of the secreted HSP70-targeted peptide APOPTIN derived from Apoptin to GBM tumors. We applied this therapy to GBM models using human U87MG glioma cells and GBM xenograft models in mice. In U87MG and U251MG cells, conditioned medium from AAV2-apoptin-derived peptide (ADP)-expressing cells induced 83% and 78% cell death. In mice bearing intracranial U87MG tumors treated with AAV2-ADP, treatment resulted in a significant decrease in tumor growth and longer survival in mice bearing orthotopic invasive GBM brain tumors. These data indicate that ssAAV2-ADP injection in the left hemisphere effectively prevented ipsilateral tumor growth but was insufficient to prevent distal tumor growth in the contralateral hemisphere. However, the systemic route is the most effective approach for treating widely dispersed tumors. In summary, systemic delivery of AAV2-ADP is an attractive approach for invasive GBM treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, PR China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Daqing Oilfield General Hospital, Daqing, PR China.
authors.forename: Hengyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, PR China.
authors.forename: Songhe
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, PR China.
authors.forename: DanYang
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Daqing Oilfield General Hospital, Daqing, PR China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, PR China. Electronic address: yuanlijie1225@163.com.
authors.forename: Lijie
authors.initials: L
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D036022:Capsid Proteins / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D036022:Capsid Proteins; D018840:HSP70 Heat-Shock Proteins; C091717:VP3 protein, Chicken anemia virus
keywords: AAV2; Apoptin; Apoptin-derived-peptide (ADP); Glioma; HSP70