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

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dc.contributor.authorRoa Strauch, Juan Carlos Enrique
dc.contributor.authorViscarra, Tamara.
dc.contributor.authorBuchegger, Kurt.
dc.contributor.authorJofre, Ignacio.
dc.contributor.authorRiquelme, Ismael.
dc.contributor.authorZanella, Louise.
dc.contributor.authorAbanto, Michel.
dc.contributor.authorParker, Alyssa C.
dc.contributor.authorPiccolo, Stephen R.
dc.contributor.authorIli, Carmen.
dc.date.accessioned2019-10-17T15:22:29Z
dc.date.available2019-10-17T15:22:29Z
dc.date.issued2019
dc.date.updated2019-10-14T19:12:49Z
dc.description.abstractAbstract 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/β-catenin and integrin signaling pathway are the main metabolic pathway dysregulated in CBDCA-resistant A2780 cells.
dc.fuente.origenBiomed Central
dc.identifier.citationBiological Research. 2019 Mar 21;52(1):13
dc.identifier.doi10.1186/s40659-019-0220-0
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/26767
dc.issue.numeroNo. 13
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final13
dc.pagina.inicio1
dc.revistaBiological Researches_ES
dc.rightsacceso abierto
dc.rights.holderThe Author(s)
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.otherCáncer de ovarioes_ES
dc.subject.otherCáncer de ovario - Quimioterapiaes_ES
dc.subject.otherMedicamentos - Evaluaciónes_ES
dc.titleFunctional and transcriptomic characterization of carboplatin-resistant A2780 ovarian cancer cell linees_ES
dc.typeartículo
dc.volumenVol. 52
sipa.codpersvinculados84743
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