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Decreased functional activity of multidrug resistance protein in primary colorectal cancer

Tamás Micsik1,2, András Lőrincz3,4, Tamás Mersich5

  • 11st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085, Budapest, Hungary. micsikt@gmail.com.

Diagnostic Pathology
|April 18, 2015
PubMed
Abstract

Insights

Multidrug Resistance Protein 1 (MDR1) activity is lower in colorectal cancer cells than in healthy cells, challenging the belief that MDR1 modulates chemosensitivity. This suggests MDR1 may not be a primary factor in drug resistance for colorectal cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • ATP-Binding Cassette (ABC)-transporters MultiDrug Resistance Protein 1 (MDR1) and Multidrug Resistance Related Protein 1 (MRP1) are expressed in enterocytes and implicated in colorectal cancer chemosensitivity.
  • Previous studies on MDR1 and MRP1 expression in colorectal cancer have yielded conflicting results.
  • This study investigates the functional activity of MDR1 and MRP1 in normal enterocytes versus colorectal cancer cells.

Purpose of the Study:

  • To compare the functional activity of MDR1 and MRP1 transporters in normal human enterocytes and colorectal cancer cells.
  • To clarify the role of MDR1 and MRP1 in the chemosensitivity of colorectal cancer.

Main Methods:

  • Surgical biopsies from 100 colorectal cancer and 28 adjacent healthy mucosa samples were analyzed.
  • The modified calcein-assay was used to determine the functional activity of MDR1 and MRP1 in viable epithelial and cancer cells.
  • Statistical analysis was performed on data from 73 cancer and 11 healthy mucosa samples.

Main Results:

  • A significant decrease in mean MDR1 activity was observed in primary colorectal cancer samples compared to normal mucosa.
  • Mean MRP1 activity showed no significant difference between cancer and normal tissues.
  • Tumor stage, grade, gender, age, and location did not affect the functional activity of these transporters.

Conclusions:

  • Contrary to prevailing beliefs, MDR1 activity is lower in colorectal cancer cells than in adjacent healthy tissue, suggesting it may not play a major role in primary drug resistance.
  • The findings may explain the selective activity of certain chemotherapeutic agents like Irinotecan and Oxaliplatin.
  • Further research is needed to understand the impact of chemotherapy on MDR activity and the role of MDR activity in colorectal cancer stem cells.

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