Effect of altered WIG-1 expression on DDP sensitivity in a DDP-resistant esophageal squamous cancer cell line

Yang Qiu1, Ying-Bo Zou, Kun Li

  • 1Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, PR China.

Insights

Wide-type p53 induced gene 1 (WIG-1) can reverse cisplatin resistance in esophageal cancer. Overexpressing WIG-1 in esophageal cancer cells reduces tumor growth and increases sensitivity to chemotherapy drugs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Esophageal cancer (EC) is a highly lethal malignancy with poor prognosis.
  • Resistance to chemotherapy, particularly cisplatin (DDP), is a major challenge in EC treatment.
  • Novel strategies to overcome DDP resistance in EC are urgently needed.

Purpose of the Study:

  • To investigate the role of wide-type p53 induced gene 1 (WIG-1) in regulating DDP sensitivity in EC.
  • To evaluate the potential of WIG-1 as a therapeutic target for overcoming DDP resistance in EC.

Main Methods:

  • Development of a DDP-resistant EC cell line (EC109/DDP).
  • In vitro and in vivo experiments to assess the effect of WIG-1 overexpression on DDP sensitivity, cell proliferation, apoptosis, and tumor growth.
  • Analysis of key protein expression levels (ERCC1, Bax, Bcl-2, P-gp, GST-π).

Main Results:

  • WIG-1 overexpression significantly reduced the IC(50) of DDP in resistant EC cells.
  • WIG-1 suppressed cell proliferation, cloning efficiency, and xenograft tumor growth.
  • Upregulation of WIG-1 increased apoptosis and decreased ERCC1 expression while increasing Bax expression.

Conclusions:

  • WIG-1 plays a crucial role in reversing DDP resistance in esophageal cancer.
  • WIG-1 may exert its effect by downregulating ERCC1 and upregulating Bax expression.
  • Targeting WIG-1 presents a promising therapeutic strategy for enhancing DDP efficacy in EC treatment.