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

Viscarra, T; Buchegger, K; Jofre, I.; Riquelme, I; Zanella L; Abanto, M; Parker, AC; Piccolo, SR; Roa, JC; Ili, C; Brebi, P

Keywords: ovarian cancer, drug resistance, carboplatin, A2780 cell line, Wnt/beta-catenin-signaling pathway, Integrin signaling pathway

Abstract

"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"

Más información

Título según WOS: Functional and transcriptomic characterization of carboplatin-resistant A2780 ovarian cancer cell line
Título según SCOPUS: Functional and transcriptomic characterization of carboplatin-resistant A2780 ovarian cancer cell line
Título según SCIELO: Functional and transcriptomic characterization of carboplatin-resistant A2780 ovarian cancer cell lines
Título de la Revista: BIOLOGICAL RESEARCH
Volumen: 52
Editorial: SOC BIOLGIA CHILE
Fecha de publicación: 2019
Idioma: en
DOI:

10.1186/s40659-019-0220-0

Notas: ISI, SCIELO, SCOPUS