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: Guohong Xin, Xinhan Zhao, Xinlei Duan, Qian Ning, Min Meng, Du Meng, Lifeng Liu
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 27 Issue 1 Pg. 77-87 (Feb 2012) ISSN: 1557-8852 [Electronic] United States
• PMID: 22242594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dendrimers
• Nylons
• Oligodeoxyribonucleotides
• Oligonucleotides, Antisense
• PAMAM-G4
• Cyclooxygenase 2

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Breast Neoplasms (genetics, pathology, therapy)
• Cell Cycle (drug effects, genetics)
• Cell Growth Processes (drug effects, genetics)
• Cell Line, Tumor
• Cyclooxygenase 2 (genetics)
• Dendrimers (pharmacology)
• Female
• Flow Cytometry
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neovascularization, Pathologic (metabolism)
• Nylons (pharmacology)
• Oligodeoxyribonucleotides (genetics, pharmacology)
• Oligonucleotides, Antisense (genetics, pharmacology)
• Transfection