In vitro antitumor activity of Ganoderma Lucidum polysaccharide associated with 5-FU metronomic chemotherapy on stem cell of head and neck squamous cell carcinoma.

• Grant number: 17/01212-2
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): November 01, 2017
• Effective date (End): April 30, 2021
• Field of knowledge: Health Sciences - Dentistry
• Principal researcher: Vanessa Soares Lara
• Grantee: Marcela Rodrigues de Camargo
• Home Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Associated research grant: 13/07245-9 - Investigation of the role of cancer stem cells and microenvironment on epithelial-to-mesenchymal transition, invasion and metastasis in oral squamous cell carcinoma, AP.JP

Abstract

About 15,490 new cases of head and neck squamous cell carcinoma (HNSCC) are estimated for 2016/2017 in Brazil. Considering the first-line treatment, about 50% of over 40 thousand cases studied in this country in 2012 were predicted to have recurrence or metastasis, with a median overall survival around 10 months. Recently, the so-called tumor initiating cells or cancer stem cells (CSC) has been identified as a major contributor to the treatment failure, recurrence and metastasis. In addition to being responsible for metastasis and relapses in most patients, CSCs are believed to be the reason for the lack of efficacy of conventional treatment methods for cancer, since this subpopulation shows escaping mechanisms against radio and chemotherapy. One of the possible escaping mechanisms of CSC is the resistance to DNA damage due to increased expression of antiapoptotic proteins (Bcl2) and drug transporters pumps (ABCB1 and ABCG2) that drive chemotherapeutic drugs out of the cells. One of the first-line treatments for these cases is the combination of monoclonal antibody with the chemotherapy drug 5-Fluoracil (5-FU), however it has not been demonstrated great effectiveness, and adverse reactions such as anemia, neutropenia, thrombocytopenia, skin reactions and sepsis considerably decrease the quality of life and increase the risk of diseases related to immunosuppression. Thus, the use of metronomic chemotherapy is an alternative to maintain effective serum levels of the drug and preventing development of resistance to it. Complementarily, different compounds with biological activities have been associated with numerous anti-tumor effects and / or immunomodulators. The edible mushroom Ganoderma lucidum (GL) has, among its many properties, the ability to prevent the invasion of tumor cells and stimulate the immune response, being able to act on ABC HNSCC protein and facilitate awareness of these cells as chemotherapy. Thus, the main objective of this study is to evaluate the in vitro effects of GL polysaccharides on antitumor activities of 5-FU low doses in the subpopulation of cancer stem cells from SCC9 line of squamous cell carcinoma.