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

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

SUBMITTER: Li L 

PROVIDER: S-EPMC4978817 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature