Differential sensitivity of prostate tumor derived endothelial cells to sorafenib and sunitinib

BMC Cancer

Alessandra Fiorio Pla²  Alessia Brossa⁵  Michela Bernardini⁶  Tullio Genova⁴  Guillaume Grolez²  Arnaud Villers³  Xavier Leroy¹  Natalia Prevarskaya²  Dimitra Gkika²  Benedetta Bussolati⁵ 

[1] Institute of Pathology, Centre de Biologie-Pathologie, CHRU de Lille, Faculté de Médecine Henri-Warembourg, Université de Lille 2, Lille, France

[2] Laboratory of Excellence, Ion Channels Science and Therapeutics, Université de Lille 1, Villeneuve d’Ascq, France

[3] Department of Urology, CHU Lille, University Lille Nord de France, F-59000 Lille, France

[4] Department of Life Science and Systems Biology, University of Torino, Torino, Italy

[5] Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Centre, University of Torino, via Nizza 52, 10126 Torino, Italy

[6] Nanostructured Interfaces and Surfaces Centre of Excellence (NIS), University of Turin, Torino, Italy

关键词: Drug resistance;    Prostate cancer;    Androgen receptor;    VEGF receptor;    Anti-angiogenic therapy;   

Others  :  1117904
DOI  :  10.1186/1471-2407-14-939

 received in 2014-06-17, accepted in 2014-12-04,  发布年份 2014

【 摘 要 】

Background

Prostate cancer is the second leading cause of male cancer death in developed countries. Although the role of angiogenesis in its progression is well established, the efficacy of anti-angiogenic therapy is not clearly proved. Whether this could depend on differential responses between tumor and normal endothelial cells has not been tested.

Methods

We isolated and characterized three lines of endothelial cells from prostate cancer and we tested the effect of Sunitinib and Sorafenib, and the combined treatment with the anti-androgen Casodex, on their angiogenic functions.

Results

Endothelial cells isolated from prostate tumors showed angiogenic properties and expression of androgen and vascular endothelial cell growth factor receptors. Sunitinib affected their proliferation, survival and motility while Sorafenib only showed a minor effect. At variance, Sunitinib and Sorafenib showed similar cytotoxic and anti-angiogenic effects on normal endothelial cells. Sorafenib and Sunitinib inhibited vascular endothelial cell growth factor receptor2 phosphorylation of prostate cancer endothelial cells, while they differentially modulated Akt phosphorylation as no inhibitory effect of Sorafenib was observed on Akt activation. The combined treatment of Casodex reverted the observed resistance to Sorafenib both on cell viability and on Akt activation, whereas it did not modify the response to Sunitinib.

Conclusions

Our study demonstrates a resistant behavior of endothelial cells isolated from prostate cancer to Sorafenib, but not Sunitinib. Moreover, it shows the benefit of a multi-target therapy combining anti-angiogenic and anti-hormonal drugs to overcome resistance.

【 授权许可】

   
2014 Fiorio Pla et al.; licensee BioMed Central Ltd.

【 图 表 】

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