MDR1/P-glycoprotein and MRP-1 drug efflux pumps in pancreatic carcinoma

Anticancer Res. 2007 Jul-Aug;27(4B):2115-20.

Abstract

Background: Pancreatic cancer is one of the most challenging solid organ malignancies. This is due to its aggressiveness, frequent late presentation as advanced disease and chemoresistance. A better understanding of the molecular basis of its drug resistance is needed.

Materials and methods: In this study, the first of its kind, the expression of both MDR1 P-gp and MRP-1 protein in pancreatic tumour specimens was examined by immunohistochemistry. Expression of these drug efflux pumps was examined using semi-quantitative immunohistochemistry according to the percentage of cells within the tumour, demonstrating another staining intencity.

Results: Overall, 93.3% of pancreatic carcinomas expressed MDR1 P-gp, approximately 31% co-expressed MRP-1 with MDR1 P-gp, while 6.7% expressed neither of these proteins.

Conclusion: Our results show that drug efflux pumps, in particular that of MDR1 P-gp, are frequently expressed in pancreatic cancer. While a causative role for these efflux pumps in pancreatic cancer chemoresistance cannot necessarily be concluded, the information presented here should be considered when selecting chemotherapy/drug efflux pump inhibitors for future therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adenocarcinoma / metabolism
  • Adult
  • Aged
  • Carcinoma, Neuroendocrine / metabolism
  • Cholangiocarcinoma / metabolism
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / biosynthesis
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Pancreatic Neoplasms / metabolism*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Multidrug Resistance-Associated Proteins
  • multidrug resistance-associated protein 1