Effect of altered WIG-1 expression on DDP sensitivity in a DDP-resistant esophageal squamous cancer cell line.
Esophageal cancer (EC) is the most common esophageal malignancy and has a dismal prognosis. Developing novel strategies to reverse the resistance to chemotherapeutics in EC is currently of intense interest. The wide-type p53 induced gene 1 (WIG-1) is a p53-regulated transcription factor. The effect of WIG-1 on the regulation of cisplatin (DDP) sensitivity was evaluated in DDP-resistant EC cells both in vitro and in vivo. The DDP-resistant sub-line EC109/DDP was successfully selected following eight months of culture. Overexpression of WIG-1 in EC109/DDP cells significantly lowered the IC(50) of DDP to 1.11 ± 0.54 μg/ml when compared to Control cells (4.57 ± 0.98 μg/ml, P < 0.05). In addition, WIG-1 exerted a negative effect on cell proliferation and on the cloning efficiency of EC109/DDP cells. A significant increase in the apoptosis index and in TUNEL-positive nuclei was observed when the expression of WIG-1 was upregulated. Furthermore, WIG-1-overexpressing DDP-resistant EC cells exhibited suppressed xenograft tumor growth and a lower green fluorescent protein (GFP) fluorescence intensity following DDP injection. WIG-1 also reduced the expression of ERCC1 and increased the expression of Bax in DDP-resistant EC cells, while the expression of Bcl-2, P-gp and GST-π was not significantly altered after up- or down-regulation of WIG-1. In summary, these results show that WIG-1 may reverse the DDP resistance of EC cells by reducing ERCC1 expression and increasing Bax expression. This study will provide a framework for understanding the mechanism of DDP resistance by WIG-1 and will aid in the therapeutic use of DDP in ESCC.
Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, PR China.
Yang
Y
Qiu
Ying-Bo
YB
Zou
Kun
K
Li
Yao-Guang
YG
Jiang
Kang
K
Yang
Yun-Ping
YP
Zhao
Wei
W
Guo
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C436503:ZMAT3 protein, human; D002945:Cisplatin