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

Autor: Almeida LY; Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil., Moreira FDS; Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil., Santos GASD; School of Medicine, University of Ribeirão Preto (UNAERP), Ribeirão Preto, Brazil., Cuadra Zelaya FJM; Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil., Ortiz CA; Hematology Division, Department of Medical Images, Hematology, and Clinical Oncology, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, Brazil., Agostini M; Department of Oral Diagnosis and Pathology, School of Dentistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Mariano FS; Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil., Bastos DC; Department of Biosciences, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil., Daher URN; Department of Clinical Oncology, A. C. Camargo Cancer Center, São Paulo, Brazil.; Department of Clinical Oncology, Hospital Amaral Carvalho, São Paulo, Brazil., Kowalski LP; Department of Otorhinolaryngology and Head and Neck Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil.; Department of Head and Neck Surgery, Medical School, University of São Paulo, São Paulo, Brazil., Coletta RD; Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil., Graner E; Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil.
Jazyk: angličtina
Zdroj: Oral diseases [Oral Dis] 2023 Mar; Vol. 29 (2), pp. 649-660. Date of Electronic Publication: 2021 Sep 29.
DOI: 10.1111/odi.14017
Abstrakt: 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.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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