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The role of doxorubicin in non-viral gene transfer in the lung
- Source :
-
Biomaterials . Apr2009, Vol. 30 Issue 10, p1971-1977. 7p. - Publication Year :
- 2009
-
Abstract
- Abstract: Proteasome inhibitors have been shown to increase adeno-associated virus (AAV)-mediated transduction in vitro and in vivo. To assess if proteasome inhibitors also increase lipid-mediated gene transfer with relevance to cystic fibrosis (CF), we first assessed the effects of doxorubicin and N-acetyl-l-leucinyl-l-leucinal-l-norleucinal in non-CF (A549) and CF (CFTE29o-) airway epithelial cell lines. CFTE29o- cells did not show a response to Dox or LLnL; however, gene transfer in A549 cells increased in a dose-related fashion (p <0.05), up to approximately 20-fold respectively at the optimal dose (no treatment: 9.3×104 ±1.5×103, Dox: 1.6×106 ±2.6×105, LLnL: 1.9×106 ±3.2×105 RLU/mg protein). As Dox is used clinically in cancer chemotherapy we next assessed the effect of this drug on non-viral lung gene transfer in vivo. CF knockout mice were injected intraperitoneally (IP) with Dox (25–100mg/kg) immediately before nebulisation with plasmid DNA carrying a luciferase reporter gene under the control of a CMV promoter/enhancer (pCIKLux) complexed to the cationic lipid GL67A. Dox also significantly (p <0.05) increased expression of a plasmid regulated by an elongation factor 1α promoter (hCEFI) approximately 8-fold. Although administration of Dox before lung gene transfer may not be a clinically viable option, understanding how Dox increases lung gene expression may help to shed light on intracellular bottle-necks to gene transfer, and may help to identify other adjuncts that may be more appropriate for use in man. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 01429612
- Volume :
- 30
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 36477830
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2008.12.037