Effetti degli inibitori delle Aurora chinasi (VX-680, SNS314, ZM447439) nei tumori corticosurrenalici.

Background: Adrenocortical tumors (ACT) include benign and malignant forms. Adrenocorticla 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). Materials and Methods: Diverse biomolecular assays were performed on SW13 and H295R cells using AK inhibitors at different time 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 adenoma, 6 non-secreting adenoma and 8 normal adrenal tissues. Results: AK inhibitors significantly reduced SW13 cell viability at 72h. 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 provide 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 are considered a metastatic depot in adrenal cortex. On the contrary H295R cells showed drug resistance, which may not be imputable to genetic background. Further analysis are needed to elucidate this distinctive behaviour of H295R cells.