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Article

Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line

by
Raimonda Kubiliūtė
1,2,3,
Indrė Šulskytė
2,
Kristina Daniūnaitė
1,2,3,
Rimantas Daugelavičius
2 and
Sonata Jarmalaitė
1,3,*
1
Division of Human Genome Research Centre, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania
2
Department of Biochemistry, Faculty of Natural Sciences, Vytautas Magnus University, Kaunas, Lithuania
3
National Cancer Institute, Vilnius, Lithuania
*
Author to whom correspondence should be addressed.
Medicina 2016, 52(5), 298-306; https://doi.org/10.1016/j.medici.2016.09.003
Submission received: 5 May 2016 / Revised: 13 September 2016 / Accepted: 15 September 2016 / Published: 29 September 2016

Abstract

Background and aim: Resistance to chemotherapy is the key obstacle to the effective treat- ment of various cancers. Accumulating evidence suggests significant involvement of the epithelial-to-mesenchymal transition (EMT) in the chemoresistance of most cancer types. This study aimed at analyzing the gene expression profile of doxorubicin (DOX)-resistant colorectal cancer cells CX-1.
Materials and methods: DOX-resistant CX-1 cell sublines were acquired by stepwise increment of DOX concentrations in cell growth media. Global gene expression profiling was performed using human gene expression microarrays. The expression levels of individual genes were assessed by means of quantitative PCR (qPCR), while the DNA methylation pattern of several selected genes was determined by methylation-specific PCR.
Results: Four DOX-resistant CX-1 sublines were established as a valuable tool for cell chemoresistance studies. Altered expression of the EMT, cell adhesion and motility, and chemoresistance-related genes was observed in DOX-resistant cells by genome-wide gene expression analysis. Besides, early and significant upregulation of the key EMT genes ZEB1 (5.8×; P < 0.001) and CDH2 (6.2×; P = 0.044) was identified by qPCR, with subsequent activation of drug transporter gene ABCC1 (3.3×; P = 0.007) and cell stemness gene NANOG (2.4×; P = 0.008). Downregulation of TET1 (2.1×; P = 0.041) and changes in the methylation status of the p16 gene were also involved in the acquisition of cell resistance to DOX.
Keywords: Colon cancer; CX-1; Doxorubicin resistance; Epithelial-to-mesenchymal transition Colon cancer; CX-1; Doxorubicin resistance; Epithelial-to-mesenchymal transition

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MDPI and ACS Style

Kubiliūtė, R.; Šulskytė, I.; Daniūnaitė, K.; Daugelavičius, R.; Jarmalaitė, S. Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line. Medicina 2016, 52, 298-306. https://doi.org/10.1016/j.medici.2016.09.003

AMA Style

Kubiliūtė R, Šulskytė I, Daniūnaitė K, Daugelavičius R, Jarmalaitė S. Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line. Medicina. 2016; 52(5):298-306. https://doi.org/10.1016/j.medici.2016.09.003

Chicago/Turabian Style

Kubiliūtė, Raimonda, Indrė Šulskytė, Kristina Daniūnaitė, Rimantas Daugelavičius, and Sonata Jarmalaitė. 2016. "Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line" Medicina 52, no. 5: 298-306. https://doi.org/10.1016/j.medici.2016.09.003

APA Style

Kubiliūtė, R., Šulskytė, I., Daniūnaitė, K., Daugelavičius, R., & Jarmalaitė, S. (2016). Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line. Medicina, 52(5), 298-306. https://doi.org/10.1016/j.medici.2016.09.003

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