Next Article in Journal
Periodontal status in 18-year-old Lithuanian adolescents: An epidemiological study
Previous Article in Journal
Impact of hypertension on postreperfusion left ventricular recovery in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease
Medicina is published by MDPI from Volume 54 Issue 1 (2018). Articles in this Issue were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence. Articles are hosted by MDPI on mdpi.com as a courtesy and upon agreement with Lithuanian Medical Association, Lithuanian University of Health Sciences, and Vilnius University.
Open AccessArticle

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

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
Received: 5 May 2016 / Revised: 13 September 2016 / Accepted: 15 September 2016 / Published: 29 September 2016
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
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.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

1
Back to TopTop