Differential sensitivity of prostate tumor derived endothelial cells to sorafenib and sunitinib
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- 作者：Alessandra Fiorio Pla (47) (48) (49) (50)
Alessia Brossa (46)
Michela Bernardini (47) (48)
Tullio Genova (47)
Guillaume Grolez (49) (50)
Arnaud Villers (51)
Xavier Leroy (52)
Natalia Prevarskaya (49) (50)
Dimitra Gkika (49) (50)
Benedetta Bussolati (46)
47. Department of Life Science and Systems Biology ; University of Torino ; Torino ; Italy
48. Nanostructured Interfaces and Surfaces Centre of Excellence (NIS) ; University of Turin ; Torino ; Italy
49. Inserm U1003 ; Equipe labellis茅e par la Ligue Nationale contre le cancer ; Universit茅 des Sciences et Technologies de Lille (USTL) ; Villeneuve d鈥橝scq ; France
50. Laboratory of Excellence ; Ion Channels Science and Therapeutics ; Universit茅 de Lille 1 ; Villeneuve d鈥橝scq ; France
46. Department of Molecular Biotechnology and Health Sciences ; Molecular Biotechnology Centre ; University of Torino ; via Nizza 52 ; 10126 ; Torino ; Italy
51. Department of Urology ; CHU Lille ; University Lille Nord de France ; F-59000 ; Lille ; France
52. Institute of Pathology ; Centre de Biologie-Pathologie ; CHRU de Lille ; Facult茅 de M茅decine Henri-Warembourg ; Universit茅 de Lille 2 ; Lille ; France - 关键词：Anti ; angiogenic therapy ; VEGF receptor ; Androgen receptor ; Prostate cancer ; Drug resistance
- 刊名：BMC Cancer
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：14
- 期：1
- 全文大小：1,493 KB
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43. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/939/prepub - 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
- 出版者：BioMed Central
- ISSN：1471-2407
文摘
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.