Clinical & Experimental Metastasis

, Volume 23, Issue 2, pp 135–147 | Cite as

Sequence- and concentration-dependent effects of acute and long-term exposure to the bisphosphonate ibandronate in combination with single and multiple fractions of ionising radiation doses in human breast cancer cell lines

  • Fabrice Journé
  • Nicolas Magné
  • Carole Chaboteaux
  • Eric Kinnaert
  • Frieder Bauss
  • Jean-Jacques Body


Both bisphosphonates and radiotherapy are highly effective for the management of bone metastases. Our in vitro study examined the cytotoxic effects resulting from combinations of ibandronate and ionising radiations (RX) in various sequences on breast cancer cells. Single radiation doses were given before, at halftime of, or after acute ibandronate incubation (48 h). Single or fractionated radiation doses were applied at the end of chronic ibandronate incubation (5 weeks). Combination of acute ibandronate exposure and single radiation doses led to synergistic cytotoxic effects in MDA-MB-231 cell line, but only with low ibandronate concentrations in MCF-7 cell line. In both cell lines, synergy was more marked when ibandronate followed RX. After long-term ibandronate exposure, only high single radiation doses induced synergistic effects in MDA-MB-231 cell line. Synergy was only detected with low ibandronate concentrations in MCF-7 cell line. In both cell lines, fractionated radiation doses exerted similar effects. The combination of ibandronate with radiation can exert synergistic effects on the inhibition of breast cancer cells growth, depending on cell line, drug sequence and dosage. Our data might provide a rationale for associating bisphosphonates and radiotherapy for the treatment of bone metastases from breast cancer.


Bisphosphonate Bone metastases Breast cancer cells Ibandronate Ionising radiation 


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This study received financial support from F. Hoffmann-La Roche AG (Basel, Switzerland), from the “Fondation Medic”, from the Belgian Fund for Medical Scientific Research (grant no. 3.4563.02), from the “Fonds Lambeau-Marteaux”, and from “Les Amis de l’Institut Bordet”.


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Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Fabrice Journé
    • 1
  • Nicolas Magné
    • 2
  • Carole Chaboteaux
    • 1
  • Eric Kinnaert
    • 3
  • Frieder Bauss
    • 4
  • Jean-Jacques Body
    • 1
  1. 1.Department of Internal MedicineInstitut Jules Bordet, Centre des Tumeurs de l'Université Libre de BruxellesBrusselsBelgium
  2. 2.Department of Radiotherapy, Institut Jules BordetCentre des Tumeurs de l’Université Libre de BruxellesBrusselsBelgium
  3. 3.LOCEInstitut Jules Bordet, Centre des Tumeurs de l’Université Libre de BruxellesBrusselsBelgium
  4. 4.Pharma Research PenzbergRoche Diagnostics GmbHPenzbergGermany

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