Molecular mechanism based of Nintedanib on prostate cancer therapy

Abstract

Prostate cancer is the most common type of cancer in men and the second leading cause of death, particularly in men over 50 years old. This disease has been widely studied due to the large number of individuals affected by this type of injury, in addition to the cancer development complexity, considering the important epithelial-stromal interaction as a primary factor for alterations. Proliferating cells show increased demand for nutrients and oxygen, triggering angiogenesis which participates in critical process of growth, progression and tumor metastasis. Therefore, attention has been paid to angiogenesis inhibitors such as Nintedanib (BIBF 1120), which has shown good antitumor activity, inhibiting cell proliferation and tumor growth, due to its combined action on tumor cells, endothelial cells and pericytes. Furthermore, this drug also showed anti-inflammatory potential in idiopathic pulmonary fibrosis therapy. Therefore, the aim of this project is to decipher the molecular mechanism of Nintedanib therapy against prostate cancer, both in vitro and in vivo xenograft mouse models. For this, human prostate cell lines will be treated with the drug and submitted to invasion, clonogenic, apoptosis and flow cytometry assays, besides western immunoblotting, immunofluorescence and real-time PCR. Furthermore, in xenograft studies, PC-3 tumor xenograft will be grow subcutaneously in nude mice and the animal will be treated with Nintedanib; tumors will be excised and submitted to immunohistochemical and immunoblot analyses.