FBXW7 Enhances Cisplatin-Induced Apoptosis in Oral Cancer Cell Lines

Abstract

ABSTRACT: Background: About one-third of patients with oral squamous cell carcinoma (OSCC) have a risk of occurrence and chemoresistance, making survival rates abysmal. We aim to evaluate the role of F-box/WD repeat-containing protein 7 (FBXW7) to further develop efficient treatment of chemoresistant OSCC. Methods: FBXW7 overexpression was induced in human OSCC cell lines including SCC9 and CAL27 by a lentiviral vector, Lv-FBXW7 or lv-NC (noncoding control), and overexpression efficiency was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot of FBXW7. Cell viability was measured using MTT assay. The effects of FBXW7 overexpression on cell migration and invasion was evaluated by the colony formation assay and Matrigel assay. Apoptosis of cells with lv-FBXW7 transfection was measured by qRT-PCR and western blot analyses of BAX, BAK, MCL1, and BCL2 expression. Growth rate and cisplatin sensitivity of CAL27 xenografts with or without FBXW7 overexpression was monitored. Ki-67 and PCMA levels—which are biomarkers of intratumoural apoptosis—BAX, MCL1, Beclin1, and LC3I&II—which are autophagy biomarkers—were assessed. Results: Transfection of lv-FBXW7 in SCC9 and CAL27 cells resulted in increased sensitivity to cisplatin treatment, as evidenced by slower cell proliferation, lower colony formation and invasion, higher apoptosis, and autophagy compared to those transfected with lv-NC. Mice with CAL27 xenografts overexpressing FBXW7 also demonstrated slower tumour growth and upregulation in Ki067 and PCNA. Tumours also showed higher apoptosis and autophagy activities. Conclusions: FBXW7 overexpression was herein shown to effectively sensitise OSCC cells to cisplatin treatment in vitro and in vivo.

Keywords

• Oral squamous cell carcinoma
• FBXW7
• Chemoresistance
• Cisplatin