FASN inhibition sensitizes metastatic OSCC cells to cisplatin and paclitaxel by downregulating cyclin B1

Author(s):Show less -

de Almeida, Luciana Yamamoto ^[1] ; Moreira, Fernanda Dos Santos ^[1] ; Silva Dos Santos, Guilherme Augusto ^[2] ; Maria Cuadra Zelaya, Florence Juana ^[1] ; Ortiz, Cesar Alexander ^[3] ; Agostini, Michelle ^[4] ; Mariano, Flavia Sammartino ^[1] ; Bastos, Debora Campanella ^[5] ; Nicolau Daher, Ulisses Ribaldo ^{[6, 7]} ; Kowalski, Luiz Paulo ^{[8, 9]} ; Coletta, Ricardo D. ^[1] ; Graner, Edgard ^[1]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Piracicaba Dent Sch, Dept Oral Diag, Av Limeira 901, CP 52, BR-13414018 Piracicaba, SP - Brazil

^[2] Univ Ribeirao Preto UNAERP, Sch Med, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Images Hematol & Clin Oncol, Hematol Div, Ribeirao Preto - Brazil

^[4] Fed Univ Rio de Janeiro UFRJ, Sch Dent, Dept Oral Diag & Pathol, Rio De Janeiro - Brazil

^[5] Univ Estadual Campinas, UNICAMP, Piracicaba Dent Sch, Dept Biosci, Piracicaba - Brazil

^[6] AC Camargo Canc Ctr, Dept Clin Oncol, Sao Paulo - Brazil

^[7] Hosp Amaral Carvalho, Dept Clin Oncol, Sao Paulo - Brazil

^[8] AC Camargo Canc Ctr, Dept Otorhinolaryngol & Head & Neck Surg, Sao Paulo - Brazil

^[9] Univ Sao Paulo, Med Sch, Dept Head & Neck Surg, Sao Paulo - Brazil

• Document type: Journal article
• Source: ORAL DISEASES; SEP 2021.
• Web of Science Citations: 0

Abstract

Objectives To investigate the potential effect of fatty acid synthase (FASN) inhibitor orlistat to enhance the effectiveness of chemotherapy drugs widely used to treat oral squamous cell carcinomas (OSCC), such as 5-fluorouracil, cisplatin, and paclitaxel. Methods The OSCC SCC-9 LN-1 metastatic cell line, which expresses high levels of FASN, was used for drug combination experiments. Cell viability was analyzed by crystal violet staining and automatic cell counting. Apoptosis and cell cycle were analyzed by flow cytometry with Annexin-V/7-AAD and propidium iodide staining, respectively. Cyclin B1, Cdc25C, Cdk1, FASN, and ERBB2 levels were assessed by Western blotting. Finally, cell scratch and transwell assays were performed to assess cell migration and invasion. Results Inhibition of FASN with orlistat sensitized SCC-9 LN-1 cells to the cytotoxic effects of paclitaxel and cisplatin, but not 5-fluorouracil, which was accompanied by a significant reduction in cyclin B1. The suppression of proliferation, migration, and invasion of SCC-9 LN-1 cells induced by orlistat plus cisplatin or paclitaxel was not superior to the effects of chemotherapy drugs alone. Conclusion Our results suggest that orlistat enhances the chemosensitivity of SCC-9 LN-1 cells to cisplatin and paclitaxel by downregulating cyclin B1. (AU)

• FAPESP's process: 08/57471-7 - The role of fatty acid synthase activity in apoptosis, metastasis and vasculogenesis in melanoma
• Grantee: Edgard Graner
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/25160-8 - Effects of the combined therapy orlistat/cisplatin/5-fluorouracil on the metastatic process of orthotopic tongue squamous cell carcinomas.
• Grantee: Luciana Yamamoto de Almeida
• Support Opportunities: Scholarships in Brazil - Doctorate