title: Antitumor effect of a generation 4 polyamidoamine dendrimer/cyclooxygenase-2 antisense oligodeoxynucleotide complex on breast cancer in vitro and in vivo.
abstract: Cyclooxygenase (COX)-2 plays critical roles in tumorigenesis, tumor cell growth, and angiogenesis, and inhibiting the expression of COX-2 by gene therapy has showed promising prospects. Vectors are crucial for gene therapy. Polyamidoamine (PAMAM) dendrimers are one type of nano-vectors. In this study, we synthesized a generation 4 polyamidoamine (G4PAMAM) dendrimer/COX-2 antisense oligodeoxynucleotide complex (G4PAMAM/COX-2ASODN), determined the transfection rate of G4PAMAM/COX-2ASODN on cultured breast cancer cells, assessed the cell viability, cell cycle dynamics, and cell invasiveness after transfection, and investigated the effects of G4PAMAM/COX-2ASODN on the expression of COX-2 mRNA and protein and microvessel density (MVD) levels in the tumor tissues of a breast cancer nude mouse model. The results showed that G4PAMAM/COX-2ASODN had a high transfection rate, decreased the cell viability, induced apoptosis and G0/G1 cell cycle arrest, and suppressed cell invasiveness. After treatment with G4PAMAM/COX-2ASODN, the copy number of COX-2 mRNA and protein expression in the tumor tissue were decreased markedly, MVD in the tumor tissue was also decreased, and tumor growth was restrained (p<0. 05). We conclude that COX-2ASODN can be delivered into the cultured and transplanted breast cancer cells efficiently by G4PAMAM, can reduce the expression of COX-2 mRNA and protein, and can lower the MVD of tumor tissues. The G4PAMAM/COX-2ASODN complex has antitumor properties in vitro and in vivo.
authors.affiliation: Department of Medical Oncology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Xin
authors.forename: Xinhan
authors.initials: X
authors.lastname: Zhao
authors.forename: Xinlei
authors.initials: X
authors.lastname: Duan
authors.forename: Qian
authors.initials: Q
authors.lastname: Ning
authors.forename: Min
authors.initials: M
authors.lastname: Meng
authors.forename: Du
authors.initials: D
authors.lastname: Meng
authors.forename: Lifeng
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics*; D050091:Dendrimers / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009757:Nylons / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection
chemical_list: D050091:Dendrimers; D009757:Nylons; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; C520550:PAMAM-G4; D051546:Cyclooxygenase 2