Overexpression of beta-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma

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