title: Decreased functional activity of multidrug resistance protein in primary colorectal cancer.
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.
  
  
  CONCLUSIONS
  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.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1675739129145824.
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085, Budapest, Hungary. micsikt@gmail.com.|Rational Drug Design Laboratories, Cooperative Research Center, Semmelweis University, Üllői út 26, H-1085, Budapest, Hungary. micsikt@gmail.com.
authors.forename: Tamás
authors.initials: T
authors.lastname: Micsik
authors.affiliation: Rational Drug Design Laboratories, Cooperative Research Center, Semmelweis University, Üllői út 26, H-1085, Budapest, Hungary. andras.lorincz@chemres.hu.|Hungarian Academy of Sciences,Research Centre of Natural Sciences, Institute of Molecular Pharmacology, Department of Biological Nanochemistry, Pusztaszeri út 59-67, 1025, Budapest, Hungary. andras.lorincz@chemres.hu.
authors.forename: András
authors.initials: A
authors.lastname: Lőrincz
authors.affiliation: Department of Surgery and Vascular Surgery, Uzsoki Teaching Hospital, Uzsoki street 29, H-1145, Budapest, Hungary. mersich@uzsoki.hu.
authors.forename: Tamás
authors.initials: T
authors.lastname: Mersich
authors.affiliation: Tumorgenetika Human Biospecimen Collection and Research, Kerékgyártó u. 36-38, H-1147, Budapest, Hungary. barazso@gmail.com.|1st Department of Surgery, Semmelweis University, Üllői út 78, 1082, Budapest, Hungary. barazso@gmail.com.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Baranyai
authors.affiliation: Department of Surgery and Vascular Surgery, Uzsoki Teaching Hospital, Uzsoki street 29, H-1145, Budapest, Hungary. esvany@freemail.hu.
authors.forename: István
authors.initials: I
authors.lastname: Besznyák
authors.affiliation: Department of Surgery and Vascular Surgery, Uzsoki Teaching Hospital, Uzsoki street 29, H-1145, Budapest, Hungary. dede.kristof@uzsoki.hu.
authors.forename: Kristóf
authors.initials: K
authors.lastname: Dede
authors.affiliation: Department of Surgery and Vascular Surgery, Uzsoki Teaching Hospital, Uzsoki street 29, H-1145, Budapest, Hungary. attila_zarand@hotmail.com.|1st Department of Surgery, Semmelweis University, Üllői út 78, 1082, Budapest, Hungary. attila_zarand@hotmail.com.
authors.forename: Attila
authors.initials: A
authors.lastname: Zaránd
authors.affiliation: Department of Surgery and Vascular Surgery, Uzsoki Teaching Hospital, Uzsoki street 29, H-1145, Budapest, Hungary. jakab@uzsoki.hu.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Jakab
authors.affiliation: , Podmaniczky u. 63, H-1063, Budapest, Hungary. lkrecsak@gmail.com.
authors.forename: László Krecsák
authors.initials: LK
authors.lastname: Szöllösi
authors.affiliation: Rational Drug Design Laboratories, Cooperative Research Center, Semmelweis University, Üllői út 26, H-1085, Budapest, Hungary. gykeri@vichem.hu.|MTA-SE Pathobiochemistry Research Group, Department of Medical Chemistry, Semmelweis University, Tűzoltó utca 37-47, H-1094, Budapest, Hungary. gykeri@vichem.hu.
authors.forename: György
authors.initials: G
authors.lastname: Kéri
authors.affiliation: Rational Drug Design Laboratories, Cooperative Research Center, Semmelweis University, Üllői út 26, H-1085, Budapest, Hungary. richard.schwab@kpsdx.hu.|KPS Medical Biotechnology and Healthcare Services Ltd., Retek utca. 34, H-1022, Budapest, Hungary. richard.schwab@kpsdx.hu.
authors.forename: Richard
authors.initials: R
authors.lastname: Schwab
authors.affiliation: Rational Drug Design Laboratories, Cooperative Research Center, Semmelweis University, Üllői út 26, H-1085, Budapest, Hungary. istvan.petak@kpsdx.hu.|MTA-SE Pathobiochemistry Research Group, Department of Medical Chemistry, Semmelweis University, Tűzoltó utca 37-47, H-1094, Budapest, Hungary. istvan.petak@kpsdx.hu.|KPS Medical Biotechnology and Healthcare Services Ltd., Retek utca. 34, H-1022, Budapest, Hungary. istvan.petak@kpsdx.hu.
authors.forename: István
authors.initials: I
authors.lastname: Peták
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000368:Aged; D016022:Case-Control Studies; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D049990:Membrane Transport Modulators; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1