Decreased functional activity of multidrug resistance protein in primary colorectal cancer

Tamás Micsik, A. Lőrincz, Tamás Mersich, Zsolt Baranyai, István Besznyák, Kristóf Dede, Attila Zaránd, Ferenc Jakab, László Krecsák Szöllösi, G. Kéri, Richard Schwab, I. Peták

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: The ATP-Binding Cassette (ABC)-transporter MultiDrug Resistance Protein 1 (MDR1) and Multidrug Resistance Related Protein 1 (MRP1) are expressed on the surface of enterocytes, which has led to the belief that these high capacity transporters are responsible for modulating chemosensitvity of colorectal cancer. Several immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) studies have provided controversial results in regards to the expression levels of these two ABC-transporters in colorectal cancer. Our study was designed to determine the yet uninvestigated functional activity of MDR1 and MRP1 transporters in normal human enterocytes compared to colorectal cancer cells from surgical biopsies. Methods: 100 colorectal cancer and 28 adjacent healthy mucosa samples were obtained by intraoperative surgical sampling. Activity of MDR1 and MRP1 of viable epithelial and cancer cells were determined separately with the modified calcein-assay for multidrug resistance activity and sufficient data of 73 cancer and 11 healthy mucosa was analyzed statistically. Results: Significantly decreased mean MDR1 activity was found in primary colorectal cancer samples compared to normal mucosa, while mean MRP1 activity showed no significant change. Functional activity was not affected by gender, age, stage or grade and localization of the tumor. Conclusion: We found lower MDR activity in cancer cells versus adjacent, apparently, healthy control tissue, thus, contrary to general belief, MDR activity seems not to play a major role in primary drug resistance, but might rather explain preferential/selective activity of Irinotecan and/or Oxaliplatin. Still, this picture might be more complex since chemotherapy by itself might alter MDR activity, and furthermore, today limited data is available about MDR activity of cancer stem cells in colorectal cancers.

Original languageEnglish
Article number26
JournalDiagnostic Pathology
Volume10
Issue number1
DOIs
Publication statusPublished - Apr 16 2015

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P-Glycoproteins
P-Glycoprotein
Colorectal Neoplasms
Mucous Membrane
irinotecan
oxaliplatin
ATP-Binding Cassette Transporters
Enterocytes
Neoplasms
Neoplastic Stem Cells
Multiple Drug Resistance
Drug Resistance
Reverse Transcription
Epithelial Cells
Immunohistochemistry
Biopsy
Drug Therapy
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

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Decreased functional activity of multidrug resistance protein in primary colorectal cancer. / Micsik, Tamás; Lőrincz, A.; Mersich, Tamás; Baranyai, Zsolt; Besznyák, István; Dede, Kristóf; Zaránd, Attila; Jakab, Ferenc; Szöllösi, László Krecsák; Kéri, G.; Schwab, Richard; Peták, I.

In: Diagnostic Pathology, Vol. 10, No. 1, 26, 16.04.2015.

Research output: Contribution to journalArticle

Micsik, T, Lőrincz, A, Mersich, T, Baranyai, Z, Besznyák, I, Dede, K, Zaránd, A, Jakab, F, Szöllösi, LK, Kéri, G, Schwab, R & Peták, I 2015, 'Decreased functional activity of multidrug resistance protein in primary colorectal cancer', Diagnostic Pathology, vol. 10, no. 1, 26. https://doi.org/10.1186/s13000-015-0264-6
Micsik, Tamás ; Lőrincz, A. ; Mersich, Tamás ; Baranyai, Zsolt ; Besznyák, István ; Dede, Kristóf ; Zaránd, Attila ; Jakab, Ferenc ; Szöllösi, László Krecsák ; Kéri, G. ; Schwab, Richard ; Peták, I. / Decreased functional activity of multidrug resistance protein in primary colorectal cancer. In: Diagnostic Pathology. 2015 ; Vol. 10, No. 1.
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AU - Besznyák, István

AU - Dede, Kristóf

AU - Zaránd, Attila

AU - Jakab, Ferenc

AU - Szöllösi, László Krecsák

AU - Kéri, G.

AU - Schwab, Richard

AU - Peták, I.

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