Preclinical validation of Aurora kinases-targeting drugs in osteosarcoma

E. Tavanti, V. Sero, S. Vella, M. Fanelli, F. Michelacci, L. Landuzzi, G. Magagnoli, R. Versteeg, P. Picci, C. M. Hattinger, M. Serra

Research output: Contribution to journalArticlepeer-review

Abstract

Background:Aurora kinases are key regulators of cell cycle and represent new promising therapeutic targets in several human tumours.Methods:Biological relevance of Aurora kinase-A and-B was assessed on osteosarcoma clinical samples and by silencing these genes with specific siRNA in three human osteosarcoma cell lines. In vitro efficacy of two Aurora kinases-targeting drugs (VX-680 and ZM447439) was evaluated on a panel of four drug-sensitive and six drug-resistant human osteosarcoma cell lines.Results:Human osteosarcoma cell lines proved to be highly sensitive to both drugs. A decreased drug sensitivity was observed in doxorubicin-resistant cell lines, most probably related to ABCB1/MDR1 overexpression. Both drugs variably induced hyperploidy and apoptosis in the majority of cell lines. VX-680 also reduced in vitro cell motility and soft-agar cloning efficiency. Drug association experiments showed that VX-680 positively interacts with all conventional drugs used in osteosarcoma chemotherapy, overcoming the cross-resistance observed in the single-drug treatments. Conclusion:Aurora kinase-A and-B represent new candidate therapeutic targets for osteosarcoma. In vitro analysis of the Aurora kinases inhibitors VX-680 and ZM447439 indicated in VX-680 a new promising drug of potential clinical usefulness in association with conventional osteosarcoma chemotherapeutic agents.

Original languageEnglish
Pages (from-to)2607-2618
Number of pages12
JournalBritish Journal of Cancer
Volume109
Issue number10
DOIs
Publication statusPublished - Nov 12 2013

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Preclinical validation of Aurora kinases-targeting drugs in osteosarcoma'. Together they form a unique fingerprint.

Cite this