Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line
Background and aim: Resistance to chemotherapy is the key obstacle to the effective treatment 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 ge...
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-01-01
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| Series: | Medicina |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1010660X16300581 |
| _version_ | 1797707311902359552 |
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| author | Raimonda Kubiliūtė Indrė Šulskytė Kristina Daniūnaitė Rimantas Daugelavičius Sonata Jarmalaitė |
| author_facet | Raimonda Kubiliūtė Indrė Šulskytė Kristina Daniūnaitė Rimantas Daugelavičius Sonata Jarmalaitė |
| author_sort | Raimonda Kubiliūtė |
| collection | DOAJ |
| description | Background and aim: Resistance to chemotherapy is the key obstacle to the effective treatment 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.
Conclusion: The results of our study suggest possible involvement of the key EMT and drug transporter genes in the early phase of cancer cell chemoresistance development. |
| first_indexed | 2024-03-12T06:05:31Z |
| format | Article |
| id | doaj.art-2baac873773f42abbeee3f30772c5618 |
| institution | Directory Open Access Journal |
| issn | 1010-660X |
| language | English |
| last_indexed | 2024-03-12T06:05:31Z |
| publishDate | 2016-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-2baac873773f42abbeee3f30772c56182023-09-03T03:40:57ZengMDPI AGMedicina1010-660X2016-01-0152529830610.1016/j.medici.2016.09.003Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell lineRaimonda Kubiliūtė0Indrė Šulskytė1Kristina Daniūnaitė2Rimantas Daugelavičius3Sonata Jarmalaitė4Division of Human Genome Research Centre, Faculty of Natural Sciences, Vilnius University, Vilnius, LithuaniaDepartment of Biochemistry, Faculty of Natural Sciences, Vytautas Magnus University, Kaunas, LithuaniaDivision of Human Genome Research Centre, Faculty of Natural Sciences, Vilnius University, Vilnius, LithuaniaDepartment of Biochemistry, Faculty of Natural Sciences, Vytautas Magnus University, Kaunas, LithuaniaDivision of Human Genome Research Centre, Faculty of Natural Sciences, Vilnius University, Vilnius, LithuaniaBackground and aim: Resistance to chemotherapy is the key obstacle to the effective treatment 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. Conclusion: The results of our study suggest possible involvement of the key EMT and drug transporter genes in the early phase of cancer cell chemoresistance development.http://www.sciencedirect.com/science/article/pii/S1010660X16300581Colon cancerCX-1Doxorubicin resistanceEpithelial-to-mesenchymal transition |
| spellingShingle | Raimonda Kubiliūtė Indrė Šulskytė Kristina Daniūnaitė Rimantas Daugelavičius Sonata Jarmalaitė Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line Medicina Colon cancer CX-1 Doxorubicin resistance Epithelial-to-mesenchymal transition |
| title | Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line |
| title_full | Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line |
| title_fullStr | Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line |
| title_full_unstemmed | Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line |
| title_short | Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line |
| title_sort | molecular features of doxorubicin resistance development in colorectal cancer cx 1 cell line |
| topic | Colon cancer CX-1 Doxorubicin resistance Epithelial-to-mesenchymal transition |
| url | http://www.sciencedirect.com/science/article/pii/S1010660X16300581 |
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