Analysis of the effects of chronic stress and the neuroendocrine regulation of oral cancer

• Grant number: 11/06405-7
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2012
• End date: February 28, 2014
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Sandra Helena Penha de Oliveira
• Grantee: Sandra Helena Penha de Oliveira
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Studies have shown that chronic stress may influence the cancer development and progression. Recent research from our laboratory in an in vitro model showed strong evidence that stress hormones may directly affect the human squamous cell carcinoma (OSCC) cells behavior. To deepen understanding of this possible association, the proposal of this study is evaluate the effects of chronic stress on oral carcinogenesis in a more complex biological model. Will be used 150 male Wistar rats to evaluate the effects of chronic stress by restraint and social isolation on the tonque SCC promotion and progression induce d by carcinogen 4NQO. The physiological parameters of chronic stress will be assessed by measuring cortisol and norepinephrine plasma levels and by analyzing their concentrations in adrenal glands and tumor tissue. If evidences are found in relation the participation of chronic stress on oral carcinogenesis, we will evaluate which molecular markers can be regulated by stress-related neurohormonal mediators and contribute for induction of the malignant phenotype. Quantitative real-time PCR and ELISA will be used to measure the IL-6, EGF, TNF-± and IL-8 expression in tumor tissue and their concentrations in plasma, respectively. Expressions of ß1 and ß2-adrenergic receptors (ß-ARs), STAT3, MMP2, MMP9, VEGF, p53, p16, Ki-67 and Bcl-2 will be analyzed by immunohistochemistry. To assess whether hormones stress regulate the STAT3 production in OSCC cells (SCC9 and SCC25) western blot assay will be perform. Finally, RNAi assays will be perform to evaluate the role of STAT3 in the effects of hormones stress on IL-6 and EGF expresssion, proliferation, invasion and apoptosis of the OSCC cells. We believe that further analysis as this will offer a better understanding of the real effects of chronic stress on oral cancer and to will permit to establish new scientific basis for the future. (AU)