title: Overexpression of β-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma.
abstract: Abnormal expression of β-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression of β-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect of β-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines with β-catenin knockin and knockdown. In this study, we found that higher expression level of β-catenin can be observed in CDDP-treated cell lines as compared with the control group. Furthermore, the expression levels of β-catenin increased in both a concentration- and time-dependent manner with the cisplatin treatment. More importantly, the nuclear translocation of β-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 β-catenin in the chemoresistance of OSCC in vitro and in vivo. Our findings indicated that overexpression of β-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 in β-catenin-mediated drug resistance. Our findings indicate that the Wnt/β-catenin signaling pathway may play important roles in cisplatin resistance in OSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510074, China.
authors.forename: Long
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510074, China.
authors.forename: Hai-Chao
authors.initials: HC
authors.lastname: Liu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510074, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510074, China.
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510074, China.
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Hu
authors.affiliation: Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510074, China; Department of Oral Pathology, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Xie
authors.affiliation: Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510074, China.
authors.forename: Lanhai
authors.initials: L
authors.lastname: Lü
authors.affiliation: Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510074, China; Department of Oral Pathology, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
authors.forename: Xiaohua
authors.identifier: 0000-0003-0405-3153
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510074, China.
authors.forename: Hong-Zhang
authors.identifier: 0000-0003-1763-7238
authors.initials: HZ
authors.lastname: Huang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; D009363:Neoplasm Proteins; D051176:beta Catenin; D002945:Cisplatin