Effect of bortezomib on human neuroblastoma: analysis of molecular mechanisms involved in cytotoxicity

doi:10.1186/1476-4598-7-50

Molecular Cancer

Volume 7

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Combaret V
Boyault S
Iacono I
Brejon S
Rousseau R
Puisieux A

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Boyault S
Iacono I
Brejon S
Rousseau R
Puisieux A
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Research

Effect of bortezomib on human neuroblastoma: analysis of molecular mechanisms involved in cytotoxicity

Valérie Combaret¹ , Sandrine Boyault¹ , Isabelle Iacono¹ , Stéphanie Brejon¹ , Raphaël Rousseau²^,3^,4 and Alain Puisieux¹^,4^,5

¹Laboratoire de Recherche Translationnelle, Centre Léon Bérard, Lyon, France

²Institut d'Hématologie-Oncologie Pédiatrique, Lyon, F-69008, France

³Faculté de Médecine Lyon-Nord, Université Claude Bernard, Lyon 1, Lyon, France

⁴Inserm, U590, Lyon, France

⁵ISPB, Université de Lyon, Lyon 1, Lyon, France

author email corresponding author email

Molecular Cancer 2008, 7:50doi:10.1186/1476-4598-7-50


Published:	5 June 2008

Abstract

Background

Bortezomib, a specific and selective inhibitor of the 26S proteasome with antitumor activity against a wide range of malignancies, has been approved for the treatment of relapsed or refractory multiple myeloma and other cancers. Recently, bortezomib has been identified as an effective inhibitor of neuroblastoma cell growth and angiogenesis.

Results

In the present study, we demonstrate that some neuroblastoma cell lines are actually resistant to bortezomib. We have sought to characterize the main pathway by which proteasome inhibition leads to apoptosis, and to define the mechanism responsible for resistance to bortezomib in neuroblastoma cells. Our results show that SB202190, an inhibitor of mitogen-activated protein kinase (MAPK) p38, enhances the ability of bortezomib to induce apoptosis by preventing the phosphorylation of the heat shock protein (HSP) 27.

Conclusion

This study opens the way to further clinical investigations and suggests a potential benefit of using a combination of bortezomib with an inhibitor of p38 MAPK for the treatment of neuroblastoma relapse.