Effects of rock kinase inhibition in the invasive potential of Ewing Sarcoma cell lines

Abstract

Cancer is the leading cause of death by disease among children and adolescents for all regions of Brazil as well as in developed countries. Among them, the Ewing Sarcoma (ES) is the second most common bone tumor. Despite survival improvements of patients with localized disease, the incidence of metastasis remains very high, and about 30-40 % of patients with disease progression will die because of chemoresistance and high invasiveness of cells. Currently, ROCKs proteins has awakened an interest as a therapeutic strategy in multiple tumor types, due to its numerous functions related to cell migration, invasion, adhesion and proliferation, processes that are essential for tumor metastasis. Thus, we propose to evaluate the expression of ROCK1 and ROCK2 genes in samples of patients with Ewing's Sarcoma, and check the effects of their in vitro inhibition in SE cell lines of by synthetic drugs, emphasizing on proliferation, migration, invasion and metastasis. We also intend to evaluate the influence of ROCKs inhibition on resistance and sensitization to treatments currently available for this tumor type, conducting along in vivo experiments in immunodeficient mice to study the therapeutic potential of ROCK inhibition in relation to tumor dissemination. (AU)