Association of copper transporter expression with platinum resistance in epithelial ovarian cancer

Anticancer Res. 2013 Apr;33(4):1409-14.

Abstract

Background: Copper transporters (CTR) also regulate the cellular transport of platinum drugs, but their role in platinum resistance of ovarian cancer has not been elucidated.

Materials and methods: CTR expression in ovarian cancer tissues resected from patients treated by platinum-based chemotherapy was evaluated immunohistochemically. CTR2 expression in ovarian cancer cells was inhibited by bathocuproine disulfonate, and the changes in cisplatin sensitivity were examined.

Results: CTR2 expression was increased in chemoresistant patients, but not significantly. However, the CTR2/CTR1 ratio was significantly increased in chemoresistant patients. Cases with positive CTR2 expression or positive CTR2/CTR1 ratio had poor prognoses. When the CTR2 expression in ovarian cancer cells was suppressed, sensitivity to cisplatin was significantly increased.

Conclusion: These data suggest that CTR2 contributes to platinum resistance in ovarian cancer. The CTR2/CTR1 ratio is a useful marker for platinum sensitivity and a potential prognostic factor in patients with ovarian cancer.

MeSH terms

  • Adenocarcinoma, Clear Cell / drug therapy
  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / mortality
  • Adenocarcinoma, Mucinous / drug therapy
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Cation Transport Proteins / metabolism*
  • Cisplatin / pharmacology*
  • Copper Transporter 1
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / mortality
  • Drug Resistance, Neoplasm*
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / mortality
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Prognosis
  • Retrospective Studies
  • SLC31 Proteins
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cation Transport Proteins
  • Copper Transporter 1
  • SLC31 Proteins
  • SLC31A1 protein, human
  • SLC31A2 protein, human
  • Cisplatin