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Functional and transcriptomic characterization of carboplatin-resistant A2780 ovarian cancer cell line

dc.contributor.authorViscarra T.
dc.contributor.authorBuchegger K.
dc.contributor.authorJofre I.
dc.contributor.authorRiquelme I.
dc.contributor.authorZanella L.
dc.contributor.authorAbanto M.
dc.contributor.authorParker A.C.
dc.contributor.authorPiccolo S.R.
dc.contributor.authorRoa J.C.
dc.contributor.authorIli C.
dc.contributor.authorBrebi P.
dc.date.accessioned2020-09-02T22:30:26Z
dc.date.available2020-09-02T22:30:26Z
dc.date.issued2019
dc.identifier10.1186/s40659-019-0220-0
dc.identifier.citation52, 1, 13-
dc.identifier.issn07176287
dc.identifier.urihttps://hdl.handle.net/20.500.12728/6590
dc.descriptionBACKGROUND: 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/β-catenin and integrin signaling pathway are the main metabolic pathway dysregulated in CBDCA-resistant A2780 cells.
dc.language.isoen
dc.publisherNLM (Medline)
dc.subjectA2780 cell line
dc.subjectCarboplatin
dc.subjectDrug resistance
dc.subjectIntegrin signaling pathway
dc.subjectOvarian cancer
dc.subjectWnt/β-catenin-signaling pathway
dc.subjectantineoplastic agent
dc.subjectcarboplatin
dc.subjecttranscriptome
dc.subjectcell death
dc.subjectdrug effect
dc.subjectdrug resistance
dc.subjectfemale
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjecthuman
dc.subjectovary tumor
dc.subjectpathology
dc.subjectphenotype
dc.subjectsequence analysis
dc.subjectsignal transduction
dc.subjecttumor cell line
dc.subjectAntineoplastic Agents
dc.subjectCarboplatin
dc.subjectCell Death
dc.subjectCell Line, Tumor
dc.subjectDrug Resistance, Neoplasm
dc.subjectFemale
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectOvarian Neoplasms
dc.subjectPhenotype
dc.subjectSequence Analysis, RNA
dc.subjectSignal Transduction
dc.subjectTranscriptome
dc.titleFunctional and transcriptomic characterization of carboplatin-resistant A2780 ovarian cancer cell line
dc.typeArticle


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