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

• Published in: British journal of cancer Vol. 94; no. 12; pp. 1837 - 1844
• Main 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
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 19.06.2006
• Subjects: Adenoviridae - physiology; Adenovirus; Adenoviruses; Antineoplastic Agents - pharmacology; Biological and medical sciences; Bone cancer; Bone surgery; Cancer research; Cancer therapies; Cell culture; Cell cycle; Cell Cycle - drug effects; Cell Line, Tumor; Chemotherapy; Cisplatin - pharmacology; Combined Modality Therapy; Diseases of the osteoarticular system; Doxorubicin - pharmacology; Gene therapy; Humans; Immunotherapy; Medical research; Medical sciences; Oncology; Oncolytic Virotherapy; Orthopedics; Osteosarcoma - therapy; Osteosarcoma - virology; Translational Therapeutics; Tumors; Tumors of striated muscle and skeleton; Netherlands; Antineoplastic agent; Cell culture; Adenoviridae; Diseases of the osteoarticular system; Virotherapy; conditionally replicative adenovirus; Doxorubicin; Osteoarticular system; primary cell cultures; Isomerases; Cancerology; combination effects; Osteosarcoma; Established cell line; Primary; Primary culture; Platinum II Complexes; DNA topoisomerase (ATP-hydrolysing); Sarcoma; Enzyme; Enzyme inhibitor; Malignant tumor; Cisplatin; Virus; Alkylating agent; Chemotherapy; Treatment; Anthracyclins; Bone
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6603189

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-Delta24RGD. 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-Delta24RGD 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-Delta24RGD 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.