Effects of the combined therapy orlistat/cisplatin/5-fluorouracil on the metastatic process of orthotopic tongue squamous cell carcinomas.

• Grant number: 12/25160-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): April 01, 2013
• Effective date (End): March 31, 2015
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Edgard Graner
• Grantee: Luciana Yamamoto de Almeida
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Fatty acid synthase (FASN) is the enzyme responsible for the de novo biosynthesis of fatty acids (FA). Its expression is high in several malignancies, including oral squamous cell carcinoma (OSCC). FASN overexpression has been associated with high recurrence rates, increased risk of metastasis, lower survival rates and consequently poor prognosis in several human cancers. Orlistat (Xenical ®) is an anti-obesity drug with anti-neoplastic properties by irreversibly inhibiting FASN. Previous studies conducted in our laboratory demonstrated that BALB/c nude mice treated with orlistat have smaller orthotopic squamous cell carcinomas of the tongue as well as significant less cervical lymph node metastases (43%), in comparison with the controls. Surgery is widely used for the treatment for OSCC, however, in advanced stages patients are included in chemoradiotherapy protocols. Cisplatin (CDDP) and 5-fluorouracil (5-FU) are drugs commonly used in the chemotherapy for several human carcinomas, including OSCC. To date, there are no studies investigating the potential use of orlistat as an adjuvant for the chemotherapy of OSCC. Therefore, in the present study, we aim to investigate whether the blockage of FASN activity with orlistat associated to CDDP and 5-FU has a synergistic effect on the rates of apoptosis and proliferation of cultured OSCC cells, as well as in the metastatic spread of orthotopic tongue SCC.

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)

AGOSTINI, MICHELLE; ALMEIDA, LUCIANA Y.; BASTOS, DEBORA C.; ORTEGA, ROSE M.; MOREIRA, FERNANDA S.; SEGUIN, FABIANA; ZECCHIN, KARINA G.; RAPOSO, HELENA F.; OLIVEIRA, HELENA C. F.; AMOEDO, NIVEA D.; et al. The Fatty Acid Synthase Inhibitor Orlistat Reduces the Growth and Metastasis of Orthotopic Tongue Oral Squamous Cell Carcinomas. MOLECULAR CANCER THERAPEUTICS, v. 13, n. 3, p. 585-595, MAR 2014. (12/25160-8, 08/57471-7, 10/51090-1)

DE ALMEIDA, LUCIANA Y.; MARIANO, FLAVIA S.; BASTOS, DEBORA C.; CAVASSANI, KAREN A.; RAPHELSON, JANNA; MARIANO, VANIA S.; AGOSTINI, MICHELLE; MOREIRA, FERNANDA S.; COLETTA, RICARDO D.; MATTOS-GRANER, RENATA O.; et al. The antimetastatic activity of orlistat is accompanied by an antitumoral immune response in mouse melanoma. Cancer Chemotherapy and Pharmacology, v. 85, n. 2, DEC 2019. (08/57471-7, 12/25160-8)

DE ALMEIDA, LUCIANA YAMAMOTO; MOREIRA, FERNANDA DOS SANTOS; SILVA DOS SANTOS, GUILHERME AUGUSTO; MARIA CUADRA ZELAYA, FLORENCE JUANA; ORTIZ, CESAR ALEXANDER; AGOSTINI, MICHELLE; MARIANO, FLAVIA SAMMARTINO; BASTOS, DEBORA CAMPANELLA; NICOLAU DAHER, ULISSES RIBALDO; KOWALSKI, LUIZ PAULO; et al. FASN inhibition sensitizes metastatic OSCC cells to cisplatin and paclitaxel by downregulating cyclin B1. ORAL DISEASES, SEP 2021. (08/57471-7, 12/25160-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ALMEIDA, Luciana Yamamoto de. Effects of the fatty acid synthase inhibitor orlistat combined with 5-fluorouracil, cisplatin or paclitaxel on oral squamous carcinoma: study in a cell line and orthotopic model. 2015. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba Piracicaba, SP.