Functional and transcriptomic characterization of carboplatin-resistant A2780 ovarian cancer cell line
Biol. Res
; 52: 13, 2019. graf
Article
Dans En
| LILACS
| ID: biblio-1011415
Responsable en Bibliothèque :
CL1.1
ABSTRACT
BACKGROUND:
Ovarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780.METHODS:
The cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 µM for 2 h. Once 20 cycles of exposure to the drug were completed, the cell cultures showed a resistant phenotype. Then, the ovarian cancer cell line A2780 was grown with 100 µM of CBDCA (CBDCA-resistant cells) or without CBDCA (parental cells). After, a drug sensitivity assay, morphological analyses, cell death assays and a RNA-seq analysis were performed in CBDCA-resistant A2780 cells.RESULTS:
Microscopy on both parental and CBDCA-resistant A2780 cells showed similar characteristics in morphology and F-actin distribution within cells. In cell-death assays, parental A2780 cells showed a significant increase in phosphatidylserine translocation and caspase-3/7 cleavage compared to CBDCA-resistant A2780 cells (P < 0.05 and P < 0.005, respectively). Cell viability in parental A2780 cells was significantly decreased compared to CBDCA-resistant A2780 cells (P < 0.0005). The RNA-seq analysis showed 156 differentially expressed genes (DEGs) associated mainly to molecular functions.CONCLUSION:
CBDCA-resistant A2780 ovarian cancer cells is a reliable model of CBDCA resistance that shows several DEGs involved in molecular functions such as transmembrane activity, protein binding to cell surface receptor and catalytic activity. Also, we found that the Wnt/3-catenin and integrin signaling pathway are the main metabolic pathway dysregulated in CBDCA-resistant A2780 cells.
Texte intégral:
1
Indice:
LILACS
Sujet Principal:
Tumeurs de l'ovaire
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Régulation de l'expression des gènes tumoraux
/
Carboplatine
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Résistance aux médicaments antinéoplasiques
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Transcriptome
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Antinéoplasiques
Type d'étude:
Prognostic_studies
Limites du sujet:
Female
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Humans
langue:
En
Texte intégral:
Biol. Res
Thème du journal:
BIOLOGIA
Année:
2019
Type:
Article