Metastasis evaluation in vitro and in vivo mediated by ROCK and miR-17 in breast cancer, in response to the treatment with melatonin and curcumin

Abstract

Breast cancer represents the most common cancer among women with a high mortality rate mainly due to the intense tumor growth and metastatic potential. The skeletal metastatic cells have a weak structure and low anchoring allows the invasiveness of cells. Both cell migration and anchorage in the substrate occur through rearrangements of the actin cytoskeleton and cell processes are regulated by external signals and intracellular effectors, including the protein associated with Rho-kinase (ROCK). The expression of ROCK is therefore related to metastasis, and its gene expression modulated by miRNAs. The miR-17 has been shown to modulate proliferation, apoptosis and metastasis in breast cancer. To control these effects, studies with melatonin (a hormone secreted by the pineal gland) and curcumin (a component of the extract of Curcuma longa L) refer to them, anti-metastatic and anti-oncostatic action. The objective of this study is to evaluate in vitro and in vivo anti-metastatic response mediated by ROCK and miR-17 by melatonin and / or curcumin in breast cancer. The molecular expression of miR-17 will be verified by real-time PCR, and the ROCK will have its molecular and protein expression assessed by real-time PCR and immunohostochemistry, respectively. In addition, it will be done the technique of computed tomography (SPECT) using Tc-99m-MDP and Tc-99m-Glucarate for assessing the extent of metastasis in animal models. The data obtained in this study may explain the likely benefits of the use of melatonin and curcumin as therapeutic agents in the treatment of breast cancer, reducing invasiveness and metastasis occurrence. (AU)