Different susceptibility of osteosarcoma cell lines and primary cells to treatment with oncolytic adenovirus and doxorubicin or cisplatin

H. C.A. Graat, M. A. Witlox, F. H.E. Schagen, G. J.L. Kaspers, M. N. Helder, J. Bras, G. R. Schaap, W. R. Gerritsen, P. I.J.M. Wuisman, V. W. Van Beusechem

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1837-1844
Number of pages8
JournalBritish journal of cancer
Volume94
Issue number12
DOIs
StatePublished - Jun 19 2006

Keywords

  • Chemotherapy
  • Combination effects
  • Conditionally replicative adenovirus
  • Osteosarcoma
  • Primary cell cultures
  • Virotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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