5-fluorouracil-related enhancement of adenoviral infection is Coxsackievirus-Adenovirus Receptor independent and associated with morphological changes in lipid membranes

Cabrele, Chiara and Vogel, Mandy and Piso, Pompiliu and Rentsch, Markus and Schroeder, Josef and Jauch, Karl W. and Schlitt, Hans J. and Beham, Alexander (2006) 5-fluorouracil-related enhancement of adenoviral infection is Coxsackievirus-Adenovirus Receptor independent and associated with morphological changes in lipid membranes. WORLD JOURNAL OF GASTROENTEROLOGY, 12 (32). pp. 5168-5174. ISSN 1007-9327,

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Abstract

AIM: To evaluate the mechanism underlying the effects of 5-Fluorouracil (5-FU) on adenoviral infection. METHODS: Low and high Coxsackievirus-Adenovirus Receptor (CAR) expressing human colon carcinoma cell lines were treated with 5-FU and two El-deleted adenoviral constructs, one transferring GFP (Ad/CMV-GFP) the other bax (Ad/CEA-bax). The number of infected cells were monitored by GFP expression. To evaluate the effects of 5-FU in a receptor free system, Ad/GFP were encapsulated in liposomes and treated with 5-FU. Ad/GFP release was estimated with PCR and infection of 293 cells with the supernatant. Electron microscopy of the Ad5-GFP-liposome complex was made to investigate morphological changes of the liposomes after 5-FU. RESULTS: Infection rates of all cell lines increased from 50% to 98% with emerging 5-FU concentrations. The enhanced viral uptake was independent of the CAR expression. Additionally, 5-FU treated liposomes released 2-2.5 times more adenoviruses. Furthermore, 5-FU-treated liposomes appeared irregular and porous-like. CONCLUSION: adenoviral uptake is enhanced in the presence of 5-FU irrespective of CAR and is associated with morphological changes in membranes making the combination of both a promising option in gene therapy. (C) 2006 The WIG Press. All rights reserved.

Item Type: Article
Uncontrolled Keywords: CANCER CELL-LINES; GENE-TRANSFER; NECK-CANCER; EXPRESSION; CHEMOTHERAPY; CISPLATIN; APOPTOSIS; EFFICACY; ONYX-015; THERAPY; 5-fluorouracil; Coxsackievirus-Adenovirus Receptor; adenoviral infection; gene therapy
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 03 Feb 2021 10:46
Last Modified: 03 Feb 2021 10:46
URI: https://pred.uni-regensburg.de/id/eprint/34156

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