title: Dissociation of E-cadherin/β-catenin complex by MG132 and bortezomib enhances CDDP induced cell death in oral cancer SCC-25 cells.
abstract: E-cadherin/β-catenin complex plays an important role in maintaining the homeostasis of tissues and regulating cell proliferation, survival and apoptosis. To address the relationships between the change of E-cadherin/β-catenin complex and cell apoptosis, human oral squamous carcinoma SCC-25 cells were used to investigate whether the dissociation of the E-cadherin/β-catenin complex was the main reason of MG132- or bortezomib-induced apoptosis. We found that MG132 or bortezomib alone induced remarkable loss of cell integrity and contact, inhibited cell growth, survival, migration and caused cell cycle arrest, intracellular ROS production. Further experiments showed that colony formations were significantly decreased by MG132 and bortezomib alone or plus cis-diaminedichloroplatinum (CDDP). Immunofluorescence staining showed that SCC-25 cells exhibited remarkable accumulations of β-catenin in cytoplasm and few E-cadherin in cell membranes after MG132 or bortezomib treatment. Western blot results showed that MG132 or bortezomib induced high accumulation of ubiquitinated proteins and activation of apoptosis related protein caspase-3. Meanwhile, the combinational use of MG132 or bortezomib with CDDP led to synergistic effects on SCC-25 cells. However, knockdown of β-catenin could decrease MG132 or bortezomib induced cell death. Taken together, our data suggest that the regulation of E-cadherin/β-catenin complex could be a promising therapeutic target to overcome the multidrug resistance of oral cancer.
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Institute of Stomatological Research, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China. Electronic address: lhlv6387@hotmail.com.
authors.forename: Lanhai
authors.initials: L
authors.lastname: Lü
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China. Electronic address: xiqiangliu@yahoo.com.
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China. Electronic address: nihaowehao@163.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China. Electronic address: 517701365@qq.com.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Hu
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China. Electronic address: wangjianning@mail.sysu.edu.cn.
authors.forename: Jianning
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China. Electronic address: huanghongzhang@tom.com.
authors.forename: Hongzhang
authors.initials: H
authors.lastname: Huang
mesh_terms: D000069286:Bortezomib / Q000633:toxicity*; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002945:Cisplatin / Q000633:toxicity*; D053960:DNA Breaks / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007976:Leupeptins / Q000633:toxicity*; D009062:Mouth Neoplasms; D051176:beta Catenin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015820:Cadherins; D007976:Leupeptins; D051176:beta Catenin; D000069286:Bortezomib; D002945:Cisplatin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Bortezomib; Chemoresistence; E-cadherin/β-catenin complex; MG132; Oral cancer