Transcriptome analysis of newly established carboplatin-resistant ovarian cancer cell model reveals genes shared by drug resistance and drug-induced EMT.
Br J Cancer
; 128(7): 1344-1359, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36717670
ABSTRACT
BACKGROUND:
In ovarian cancer (OC) therapy, even initially responsive patients develop drug resistance.METHODS:
Here, we present an OC cell model composed of variants with differing degrees of acquired resistance to carboplatin (CBP), cross-resistance to paclitaxel, and CBP-induced metastatic properties (migration and invasion). Transcriptome data were analysed by two approaches identifying differentially expressed genes and CBP sensitivity-correlating genes. The impact of selected genes and signalling pathways on drug resistance and metastatic potential, along with their clinical relevance, was examined by in vitro and in silico approaches.RESULTS:
TMEM200A and PRKAR1B were recognised as potentially involved in both phenomena, also having high predictive and prognostic values for OC patients. CBP-resistant MES-OV CBP8 cells were more sensitive to PI3K/Akt/mTOR pathway inhibitors Rapamycin, Wortmannin, SB216763, and transcription inhibitor Triptolide compared with parental MES-OV cells. When combined with CBP, Rapamycin decreased the sensitivity of parental cells while Triptolide sensitised drug-resistant cells to CBP. Four PI3K/Akt/mTOR inhibitors reduced migration in both cell lines.CONCLUSIONS:
A newly established research model and two distinct transcriptome analysis approaches identified novel candidate genes enrolled in CBP resistance development and/or CBP-induced EMT and implied that one-gene targeting could be a better approach than signalling pathway inhibition for influencing both phenomena.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Proteínas Proto-Oncogênicas c-akt
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Croácia