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Research Paper
Mechanistic Analysis and Comparison of Viral Fusogenic Membrane Proteins for their Synergistic Effects on Chemotherapy
Dennis Hoffmann, Thomas Grunwald, Seraphin Kuate and Oliver Wildner
volume 6 | issue 4
April 2007Pages: 510 - 518
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Previously we demonstrated that the expression of fusogenic membrane proteins (FMG) of measles virus (MV-H/F) can synergistically enhance chemotherapy. In this study, we used median-effect analysis to evaluate whether the expression of respira-tory syncytial virus (RSV-F), as well as vesicular stomatitis virus (VSV-G) can also synergistically enhance chemotherapy. Furthermore we elucidated by western blot analysis some molecular pathways that might be responsible for this effect. We showed in colorectal cancer cell lines that the expression of MV-H/F, but also of RSV-F, as well as VSV-G can synergistically enhance p53-independent clinically relevant chemotherapy (FOLFOX) over most of the cytotoxic dose range. In a subcu-taneous HT-29 colorectal xenograft model, we demonstrated that the administration of replication-deficient adenovirus vectors encoding MV-H/F, RSV-F or VSV-G in combination with FOLFOX significantly enhanced treatment outcome when com-pared to the treatment with each compound individually. The anti-neoplastic efficacy of RSV-F was somewhat better than that of MV-H/F and both were statistically sig-nificantly more efficacious than VSV-G alone or in combination with chemotherapy. Treatment efficacy was further significantly improved when the replication-deficient FMG encoding vectors were trans-complemented for replication with a replication-restricted oncolytic adenovirus to improve tumor transduction efficiency. The combi-nation of FMG expression, chemotherapy and trans-complementing oncolytic vectors resulted in a significantly better treatment efficacy than treatment with its components as single- or double-agent therapy. Our data indicates that FMG expression (i.e. RSV-F and MV-H/F) in combination with chemotherapy and viral oncolysis warrants further investigations.
Authors
Dennis Hoffmann
Ruhr-University Bochum, Bochum, Germany
Thomas Grunwald
Ruhr-University Bochum, Bochum, Germany
Seraphin Kuate
Ruhr-University Bochum, Bochum, Germany
Oliver Wildner
Ruhr-University Bochum, Bochum, Germany
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.