Effect of Altered WIG-1 Expression on DDP Sensitivity in a DDPResistant Esophageal Squamous Cancer Cell Line
2012
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.
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