Basic Research
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World J Gastroenterol. Aug 28, 2006; 12(32): 5168-5174
Published online Aug 28, 2006. doi: 10.3748/wjg.v12.i32.5168
5-Fluorouracil-related enhancement of adenoviral infection is Coxsackievirus-adenovirus receptor independent and associated with morphological changes in lipid membranes
Chiara Cabrele, Mandy Vogel, Pompiliu Piso, Markus Rentsch, Josef Schröder, Karl W Jauch, Hans J Schlitt, Alexander Beham
Chiara Cabrele, Mandy Vogel, Pompiliu Piso, Markus Rentsch, Josef Schröder, Karl W Jauch, Hans J Schlitt, Alexander Beham, Department of Surgery, Clinic of the Regensburg University, Franz-Josef-Strauss-Allee 11, D-93053, Regensburg, Germany
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. med. A Beham, Klinik und Poliklinik für Chirurgie , der Universität Regensburg, Klinikum Regensburg, Franz-Josef-Strauss Allee 11, 83047 Regensburg, Germany. alexander.
Telephone: +49-941- 9447995 Fax: +49-941- 9446802
Received: June 3, 2005
Revised: July 20, 2005
Accepted: July 28, 2005
Published online: August 28, 2006

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 E1-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.

Keywords: 5-Fluorouracil, Coxsackievirus-adenovirus receptor, Adenoviral infection, Gene therapy