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Article Dans Une Revue Biochemical Pharmacology Année : 2009

Impact of alendronate and VEGF-antisense combined treatment on highly VEGF-expressing A431 cells

Résumé

Bisphosphonates, and more specially nitrogen-containing bisphosphonates, which are in current use for the treatment of bone diseases, demonstrate proapoptotic, antiproliferative, antiangiogenic and anti-invasive properties on tumor cells. The amino-bisphosphonate alendronate is considered as a potential anticancer drug. In the case of A431 cells, which express high levels of VEGF, it had a two-step effect. At 24 h, the antitumor properties of alendronate were counterbalanced by a survival process, which consisted of an enhancement of VEGF expression (mRNA and protein secretion) and TGF[alpha] secretion. It was only at 48 h that alendronate displayed the expected antiproliferative and antiangiogenic properties. The first step, in which the PI3K pathway was engaged, could be prevented by the use of a VEGF-antisense oligonucleotide. The combination of such an antisense with small concentrations of alendronate (~2 [mu]M), which is of the order of clinically used concentrations, was shown to have an antiangiogenic effect as soon as 12 h.

Dates et versions

hal-00416638 , version 1 (14-09-2009)

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Citer

Medge Mongerard-Coulanges, Evelyne Migianu-Griffoni, Marc Lecouvey, Béatrice Jolles. Impact of alendronate and VEGF-antisense combined treatment on highly VEGF-expressing A431 cells. Biochemical Pharmacology, 2009, 77 (10), pp.1580-1585. ⟨10.1016/j.bcp.2009.02.016⟩. ⟨hal-00416638⟩
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