Long-term persistence of acquired resistance to 5-fluorouracil in the colon cancer cell line SW620

Journal Article · Mon Nov 15 04:00:00 EST 2010 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2010.09.003· OSTI ID:22209923

Schmidt, W. M. ^[1]; Krupitza, G. ^[2]; Steger, G. G.; Mikulits, W. ^[3]; Kortsaris, A. ^[4]; Mader, R. M. ^[3]

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1. Center for Anatomy and Cell Biology, Waehringer Strasse 13, 1090 Vienna (Austria)
2. Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)
3. Department of Medicine I, Medical University of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)
4. Department of Biochemistry, Medical School, Democritus University of Thrace, 6th km Alexandroupolis-Komotini (Dragana), 68100 Alexandroupolis (Greece)

Treatment resistance to antineoplastic drugs represents a major clinical problem. Here, we investigated the long-term stability of acquired resistance to 5-fluorouracil (FU) in an in vitro colon cancer model, using four sub-clones characterised by increasing FU-resistance derived from the cell line SW620. The resistance phenotype was preserved after FU withdrawal for 15 weeks ({approx} 100 cell divisions) independent of the established level of drug resistance and of epigenetic silencing. Remarkably, resistant clones tolerated serum deprivation, adopted a CD133{sup +} CD44{sup -} phenotype, and further exhibited loss of membrane-bound E-cadherin together with predominant nuclear {beta}-catenin localisation. Thus, we provide evidence for a long-term memory of acquired drug resistance, driven by multiple cellular strategies (epithelial-mesenchymal transition and selective propagation of CD133{sup +} cells). These resistance phenomena, in turn, accentuate the malignant phenotype.

• OSTI ID: 22209923
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 19 Vol. 316; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTINEOPLASTIC DRUGS
CELL DIVISION
IN VITRO
LARGE INTESTINE
NEOPLASMS
PHENOTYPE
STEM CELLS
URACILS