Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106


Effect of Altered WIG-1 Expression on DDP Sensitivity in a DDPResistant Esophageal Squamous Cancer Cell Line

Author(s): Yang Qiu, Ying-Bo Zou, Kun Li, Yao-Guang Jiang, Kang Yang, Yun-Ping Zhao and Wei Guo

Affiliation: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Road, Chongqing 400042, China


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 IC50 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.

Keywords: WIG-1, ESCC, EC109, DDP, drug resistance, chemotherapy

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