Cell Cycle Synchronization and Reovirus Oncolysis
Effect of Cell Cycle Synchronization on Tumor Sensitivity to Reovirus Oncolysis
Thanks Matdu on V2
Research published Sept 14th, 2010 by our great UK research team. IMO a great display of teamwork here. No doubt we are still filing IP that could have future value.
Mol Ther. 2010 Sep 14. [Epub ahead of print]
The Effect of Cell Cycle Synchronization on Tumor Sensitivity to Reovirus Oncolysis.
Heinemann L, Simpson GR, Annels NE, Vile R, Melcher A, Prestwich R, Harrington KJ, Pandha HS.
Oncology, Postgraduate Medical School, University of Surrey, Guildford, UK.
Abstract
The potential for increased sensitivity of tumor cells to oncolytic reovirus by altering the normal cell cycle using clinically available pharmacological agents was investigated.
B16.F10 mouse melanoma cells were partially synchronized with hydroxyurea, thymidine, or by mitotic shake-off. Cell survival was determined using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium)] survival assay and virus yield in tumors by plaque assay.
An enhanced sensitivity to reovirus was observed following the removal of either hydroxyurea or thymidine from the culture medium (P < 0.0001). The greatest survival difference compared to normal cycling cells was noted when the majority of cells were in S and G2/M phases, and was associated with increased viral replication. Cells collected by mitotic shake-off were nearly devoid of cells in S phase and were less susceptible to reovirus-induced cell kill than their nonsynchronized counterparts (P < 0.0001). In vivo combination of hydroxyurea followed by intratumoral reovirus resulted in reduced tumor growth and increased survival compared to monotherapy (P = 0.0041) at 15 days. Increased amounts of virus were retrieved from tumors from mice treated with sequential hydroxyurea/reovirus compared to concomitant treatment or reovirus monotherapy. These data justify clinical evaluation of this approach supported by the extensive experience, low cost, simple administration, and availability of hydroxyurea.
