Endocrine Abstracts

Introduction: Adrenocortical tumors (ACT) are common diseases mostly benign, but among them, adrenocortical carcinomas (ACC) appear highly aggressive with metastatic potential. Wnt/β-catenin pathway is frequently switched on in ACT, with β-catenin greatly dephosphorylated and consequently activated. While IWR1 induces an increase in Axin2 protein levels, XAV939 inhibits tankyrase 1 and 2 (thus stabilizing Axin): both stimulate β-catenin phosphorylation and degradation.

Aim: To investigate the role of IWR1 and XAV939 alone or in combination with mitotane in adrenocortical tumor cell lines and in primary adrenocortical tumor cells.

Methods: MTT test was performed on SW13 and H295R cells and two ACC and two cortisol producing adenomas primary cell cultures. Expression of IWR1 and XAV939 targets (Tankyrase1, Tankyrase2, Axin1 and Axin2) and β-catenin were confirmed by western blot.

Results: MTT test at 72 h revealed a concrete cell viability decrease using XAV939 (10 μM) of 52% for SW13 and 37% for H295R cells. Furthermore IWR1 at 72 h (10 μM) induced a moderate cell viability reduction for SW13 cells of 57% and for H295R cells of 30%. In SW13 cells at 72 h, combination of mitotane (10 μM) and XAV939 (10 μM) resulted in cell viability decrement of 15% if compared to XAV939 alone. No appreciably alteration was found in combination regimen for H295R cells. Furthermore XAV939 alone at 24 h was effective in 1 ACC primary cell culture, while IWR1 at 24 h showed a weak cell viability decrease in one ACC and one CPA primary cell culture.

Discussion and conclusions: Our preliminary results demonstrated the expressions of different IWR1 and XAV939 targets in adrenocortical cells. Moreover IWR1 and XAV939 seem to effectively act on Wnt/β-catenin pathway, providing evidence for their potential role on ACT treatment. Further analysis are in progress to substantiate these data.