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- Title
Different susceptibility of osteosarcoma cell lines and primary cells to treatment with oncolytic adenovirus and doxorubicin or cisplatin.
- Authors
Graat, H. C. A.; Witlox, M. A.; Schagen, F. H. E.; Kaspers, G. J. L.; Helder, M. N.; Bras, J.; Schaap, G. R.; Gerritsen, W. R.; Wuisman, P. I. J. M.; van Beusechem, V. W.
- Abstract
Despite improvements in treatment regimens for osteosarcoma (OS) patients, survival rate has not increased over the last two decades. New treatment modalities are therefore warranted. Preclinical results with conditionally replicative adenoviruses (CRAds) to treat OS are promising. One type of CRAd that was effective against OS cells is Ad5-Δ24RGD. In other types of cancer, CRAds have been shown to interact synergistically with chemotherapeutic agents. Chemotherapy for OS often includes doxorubicin and cisplatin. Therefore, we explored combination treatment of OS cell lines and primary OS cell cultures with Ad5-Δ24RGD and doxorubicin or cisplatin. On OS cell lines, combination treatment was additive to synergistic. Surprisingly, however, on seven of eight primary OS samples no such combination effects were observed. In contrast, in many cases chemotherapy even inhibited CRAd-mediated cell killing. The inhibitory effect of doxorubicin on Ad5-Δ24RGD in primary OS cells appeared to correlate with slow cell growth rate; reduced viral replication and absence of chemotherapy-induced G2 cell cycle arrest. Our results point to the possibility that, at least for OS, virotherapy and chemotherapy should best not be performed simultaneously. In general, our work underscores the importance of testing new genetic anticancer agents and treatment regimens on primary cancer specimens.British Journal of Cancer (2006) 94, 1837–1844. doi:10.1038/sj.bjc.6603189 www.bjcancer.com Published online 30 May 2006
- Subjects
OSTEOSARCOMA; BONE cancer; CANCER patients; DOXORUBICIN; DRUG therapy
- Publication
British Journal of Cancer, 2006, Vol 94, Issue 12, p1837
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1038/sj.bjc.6603189