Mitotane (MTT) is an adrenolytic drug most used in the adjuvant and advanced treatment of adrenocortical carcinoma (ACC). Radiotherapy has so far had a limited use in the treatment of this cancer but recently its use has been reconsidered in this setting. The purpose of this study will be to investigate the effect of MTT and ionizing radiations (IR) singularly and in combination with them on cell growth inhibition and cell cycle perturbation in a xenograft model of ACC.
This study will be performed in H295R cell lines and in nude mice. Nude mice will be infected with H295R cells monitoring the neoplastic growth. After tumour development, animals will be stratified into groups including not infected mice, ACC infected mice to underwent different treatments.
The development of treated and untreated tumours will be monitored by MRI analyses. After mice sacrifice, the tumours will be removed to analysing cell cycle phases and DNA synthesis by FACScan cytofluorimeter. Molecules involved in the cell cycle will be investigated by Western blot analysis. However, will be assess the steroid levels in mice treated. Moreover, inducing a mishmatch repair protein (MMR) MLH1 and MSH2 downregulation in H295R cells will be study the role of this class of enzyme in treatment used.
