Overexpression ofβ-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma

Abstract

Abnormal expression ofβ-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression ofβ-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect ofβ-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines withβ-catenin knockin and knockdown. In this study, we found that higher expression level ofβ-catenin can be observed in CDDP-treated cell lines as compared with the control group. Furthermore, the expression levels ofβ-catenin increased in both a concentration- and time-dependent manner with the cisplatin treatment. More importantly, the nuclear translocation ofβ-catenin could also be observed by confocal microscope analysis. Stable cell lines with CTNNB1 knockin and knockdown were established to further investigate the potential role and mechanism ofβ-catenin in the chemoresistance of OSCC in vitro and in vivo. Our findings indicated that overexpression ofβ-catenin promoted cisplatin resistance in OSCC in vitro and in vivo. We confirmed that GSK-3β, C-myc, Bcl-2, P-gp, and MRP-1 were involved inβ-catenin-mediated drug resistance. Our findings indicate that the Wnt/β-catenin signaling pathway may play important roles in cisplatin resistance in OSCC.