Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line
| Autor: | Rimantas Daugelavičius, Sonata Jarmalaitė, Indrė Šulskytė, Raimonda Kubiliūtė, Kristina Daniūnaitė |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Homeobox protein NANOG medicine.medical_specialty Cell Biology Epigenesis Genetic 03 medical and health sciences CX-1 Cell Movement Internal medicine Cell Line Tumor Gene expression medicine Cell Adhesion Humans Topoisomerase II Inhibitors Doxorubicin resistance Gene Oligonucleotide Array Sequence Analysis Medicine(all) lcsh:R5-920 Antibiotics Antineoplastic Gene Expression Profiling Genes p16 Cancer DNA Methylation medicine.disease Colon cancer Gene expression profiling 030104 developmental biology medicine.anatomical_structure Real-time polymerase chain reaction Epithelial-to-mesenchymal transition Doxorubicin Drug Resistance Neoplasm Automotive Engineering DNA methylation Cancer research lcsh:Medicine (General) Colorectal Neoplasms Genome-Wide Association Study |
| Zdroj: | Medicina Volume 52 Issue 5 Pages 298-306 Medicina, Vol 52, Iss 5, Pp 298-306 (2016) Medicina; Volume 52; Issue 5; Pages: 298-306 |
| ISSN: | 1010-660X |
| DOI: | 10.1016/j.medici.2016.09.003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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