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The association of Orlistat with chemotherapic agents for the treatment of oral squamous cell carcinoma: an in vitro and in vivo study in orthotopic models

Grant number: 14/20832-3
Support type:Regular Research Grants
Duration: February 01, 2015 - January 31, 2017
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Edgard Graner
Grantee:Edgard Graner
Home Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Fatty acid synthase (FASN) is the anabolic enzyme responsible for the endogenous synthesis of fatty acids. Its expression and activity is abnormally high in several human malignancies, including oral squamous cell carcinomas (OSCC). It has been consistently demonstrated that the expression of FASN is associated with higher rates of recurrence, metastatic dissemination, and poor prognosis for OSCC patients. Orlistat was initially developed and clinically used as an anti-obesity drug; however, it also has important anticancer properties due to the irreversible inhibition of FASN activity. Our group has recently shown that the systemic treatment with this drug significantly reduces the size of primary tumors and the number of regional metastases by 43% in an orthotopic model of oral tongue squamous cell carcinoma (OTSCC). The treatment of choice for OSCC is surgical resection; however, advanced cases generally receive adjuvant radiotherapy and / or chemotherapy. Cisplatin (CDDP), fluorouracil (5-FU), and paclitaxel (PTX) are widely used for the treatment of several types of cancers, including OSCC. To date, there is no information in the literature regarding the application of FASN inhibitors as adjuvants for the OSCC chemotherapy. The aim of the present research project is to evaluate the effects of the association of orlistat with CDDP, 5-FU, and PTX on the proliferation and cell death of the metastatic OSCC cell line SCC-9 ZsGreen LN1, developed in our laboratory. Synergic drug combinations in vitro will be further tested in the orthotopic OTSCC with the same cell line, in which both the primary tumors and metastatic dissemination will be analyzed. Finally, we also propose to develop OTSCC patient-derived xenografts (PDX) through the transplantation of small fragments of tumor tissues from patients attending the OROCENTRO, FOP-UNICAMP. PDX may reproduce with more fidelity the patient´s disease by representing tumor cell heterogeneity and predict individual responses to chemotherapeutic agents, their associations, and new drugs. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE AQUINO, IARA GONCALVES; BASTOS, DEBORA CAMPANELLA; MARIA CUADRA-ZELAYA, FLORENCE JUANA; TEIXEIRA, ISADORA FERRARI; SALO, TUULA; DELLA COLETTA, RICARDO; GRANER, EDGARD. Anticancer properties of the fatty acid synthase inhibitor TVB-3166 on oral squamous cell carcinoma cell lines. ARCHIVES OF ORAL BIOLOGY, v. 113, MAY 2020. Web of Science Citations: 0.
BASTOS, DEBORA C.; PAUPERT, JENNY; MAILLARD, CATHERINE; SEGUIN, FABIANA; CARVALHO, MARCO A.; AGOSTINI, MICHELLE; COLETTA, RICARDO D.; NOEL, AGNES; GRANER, EDGARD. Effects of fatty acid synthase inhibitors on lymphatic vessels: an in vitro and in vivo study in a melanoma model. LABORATORY INVESTIGATION, v. 97, n. 2, p. 194-206, FEB 2017. Web of Science Citations: 10.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.