Effects of Sorafenib, a tyrosin kinase inhibitor, on adrenal cancer.
The lack of effective medical treatment for the adrenocortical carcinoma (ACC), induce to search a better medical treatment protocols for ACC neoplasm. Based on the efficacy of sorafenib, a tyrosin kinase inhibitor, in different human tumors, the aim of this study was to understand the mechanism through which sorafenib acts on ACC and sometimes it alone is not able to induce a long-lasting antiproliferative effect in this tumor.
The effects of sorafenib will be tested on ACC primary cell culture from adrenalectomy and parallely in H295R cell line by evaluating cell viability and apoptosis and the VEGF receptor signaling, such as VE-cadherin and ß-catenin complex formation. In addition we will test the sorefenib effects on a 3D cell culture model by using the same H295R model in vitro. Cell death will be investigated and experiments of co-immunoprecipitation will be performed in order to clarify the involvement of VEGFR-VE-cadherin complex and b-catenin proteins after sorafenib treatment. The results obtained will be confirmed both by the ultrastructural analysis and by 3D model in ACC cells.