ECE2014 Poster Presentations Endocrine tumours and neoplasia (99 abstracts)
Aurora kinases inhibitors Vx-680, SNS314 and ZM447439 in adrenocortical tumors
Raffaele Pezzani 1 , Beatrice Rubin 1 , Loris Bertazza 1 , Maria Verena Cicala 1 , Susi Barollo 1 , Maurizio Iacobone 2 , Caterina Mian 1 , Carla Scaroni 1 , Salvatore Ulisse 3 & Franco Mantero 1
1Department of Medicine, UO Endocrinology, University of Padova, Padova, Italy; 2Minimally Invasive Endocrine Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; 3Department of Experimental Medicine, University of Roma
‘La Sapienza’, Roma, Italy.
Background: Adrenocortical tumors (ACT) include benign and malignant forms. Adrenocortical carcinomas (ACC) are highly malignant neoplasms with poor prognosis and strong metastatic potential. Aurora kinase family members (AK) are serine/threonine kinase involved in the regulation of mitosis. Aurora kinase A (AKA) promotes centrosome maturation and spindle assembly, while aurora kinase B (AKB) is necessary for spindle assembly checkpoint and cytokinesis.
Aim: To evaluate AK inhibitors, Vx-680, SNS314 and ZM447439 in adrenocortical cell lines (SW13 and H295R cells).
Materials and methods: Diverse biomolecular assays were performed on SW13 and H295R cells using AK inhibitors at different times and concentrations. Moreover AK expression was evaluated in 67 ACT by qRT-PCR. The cohort of patients was subdivided into 22 ACC, 14 aldosterone producing adenoma, 17 cortisol producing adenomas, six non-secreting adenomas and eight normal adrenal tissues.
Results: AK inhibitors significantly reduced SW13 cell viability at 72 h. Cell cycle distribution and clonogenic assay results were modulated by AK inhibitors in SW13 cells, as well as[3H] thymidine assay. Furthermore Vx-680 at 200 nM induced an evident decrease of AKA and AKB in SW13 cells analyzed by western blot. No appreciable change was perceived in H295R cells. Direct sequencing of AKA and AKB provided no substantial difference between SW13 and H295R cells. AK are also expressed in all tissues and indeed ACC samples overexpressed AKA (91%) and AKB (87%).
Conclusions: Our results demonstrated that AK inhibitors seem to strictly act on SW13 cells, suggesting their potential use on some malignant tumors, as SW13 cells are considered a metastatic depot in adrenal cortex. On the contrary H295R cells showed drugs resistance, which may not be imputable to genetic background. Further analysis are needed to elucidate this distinctive behavior of H295R cells.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more