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Abstract

Background: About one-third of Oral Squamous Cell Carcinoma (OSCC) patients have a risk of occurrence and chemo resistance, making the survival abysmal. We aim to evaluate the role of F-Box/WD repeat-containing protein 7 (FBXW7) to further develop efficient treatment of chemo resistant OSCC.

Methods: FBXW7 overexpression was induced by a lent viral vector, Lv-FBXW7 or lv-NC (non-coding control) and overexpression efficiency was assessed using quantitative real-time PCR (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 intra-tumoral apoptosis, BAX, MCL1, Beclin1, LC3I and 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 tumor growth and up regulation in Ki067 and PCNA. Tumors also showed higher apoptosis and autophagy activities.

Conclusion: FBXW7 overexpression was herein shown to effectively sensitize OSCC cells to Cisplatin treatment in vitro and in vivo, potentiating FBXW7 transduction as a new treatment strategy for OSCC.

Keywords: Oral squamous cell carcinoma; FBXW7; Chemo resistance; Cisplatin