MMR-proficient and MMR-deficient colorectal cancer cells: 5-Fluorouracil treatment response and correlation to CD133 and
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J Biosci (2020)45:121 DOI: 10.1007/s12038-020-00093-8
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MMR-proficient and MMR-deficient colorectal cancer cells: 5-Fluorouracil treatment response and correlation to CD133 and MGMT expression JAIME A. OLIVER1,2, , RAU´L ORTIZ2,3,4, , CRISTINA JIME´NEZ-LUNA2,3,5, LAURA CABEZA2,3,4, GLORIA PERAZZOLI2,4,6, OCTAVIO CABA2,3,4, CRISTINA MESAS2,3,4, CONSOLACIO´N MELGUIZO2,3,4* and JOSE PRADOS2,3,4 1
Center for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK
2
Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain 3
Department of Anatomy and Embryology, University of Granada, Granada, Spain
4
Biosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spain 5
Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland 6
Department of Medicine, University of Almeria, 04120 Almerı´a, Spain *Corresponding author (Email, [email protected])
These authors contributed equality to this work.
MS received 24 April 2020; accepted 25 August 2020 Cancer stem cells (CSCs) from colorectal cancer (CRC), characterized by CD133 expression, have been associated with 5-fluorouracile (5-FU) chemoresistance. DNA repair mechanisms, such as O6-alkylguanine DNA alkyltransferase (MGMT) and mismatch repair (MMR) systems, have also been correlated to 5-FU resistance in CRC. The aim of this study was to evaluate the modulation of CD133 and MGMT in MMRproficient and MMR-deficient CRC cells under 5-FU treatment and the effect of this drug in CSCs. CD133 and MGMT methylation status were determined in MMR-proficient (SW480 and HT29) and MMR-deficient (RKO and HCT116) cell lines by methylation-specific PCRs. SW480 and RKO were selected to determine modulation of CD133, MGMT and MMR expression after 5-FU treatment by qPCR. In addition, CD133, MGMT and MMR were analyze in SW480 and RKO CSCs. No association between promoter methylation and MGMT and CD133 expression was found. 5-FU treatment increased CD133 expression independently to MMR status in SW480 and RKO and was able to increase hMLH1 expression in RKO, a MMR-deficient cell line. RKO/ CSCs overexpressed CD133 and MMR (hMSH2 and hMSH6) while SW480/CSCs showed a significant increase in CD133, MMR (hMLH1, hMSH2 and hMSH6) and MGMT, moreover 5-FU resistance than parental cell lines. Thus, although CSCs 5-FU chemoresistance appears to be independently to MMR status, hMLH1 might play a key role in CSC response to 5-FU. New drugs exploding these differences could benefit the prognostic of patients with CRC. Keywords.
Cancer stem cells; CD133; colorectal cancer; 5-fluorouracil; MGMT; MMR
Electronic supplementary material: The online version of this article (https://doi.org/10.1007/s12038-020-00093-8) contains supplementary material, which is available to authorized users. http://www.ias.ac.in/jbiosci
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JA Oliver et al.
1. Introduction
2. Materials and methods
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