AKR1C3 overexpression mediates methotrexate resistance in choriocarcinoma cells.
Int J Med Sci
; 11(11): 1089-97, 2014.
Article
em En
| MEDLINE
| ID: mdl-25170291
ABSTRACT
BACKGROUND:
Chemotherapy is typically used to treat choriocarcinoma, but a small proportion of tumors develop resistance to chemotherapy. Similarly, methotrexate (MTX) is a first-line chemotherapy used to treat choriocarcinoma; although ~30% of patients are drug-resistant for MTX mono-therapy. Thus, we sought to elucidate the mechanism of chemotherapeutic-resistance of MTX.METHODS:
RNA interference technology, colony formation, and MTT assays were used to investigate the role of aldo-keto reductase family 1, member C3 (AKR1C3) in MTX resistance in choriocarcinoma cells.RESULTS:
AKR1C3 expression was higher in JeG-3R cells compared to JeG-3 cells and targeted inhibition of AKR1C3 expression with shRNA suppresses growth of choriocarcinoma cells as measured by colony formation and MTT assays. Overexpression of AKR1C3 increased chemotherapeutic resistance in JeG-3 cells. Furthermore, AKR1C3 silencing increases sensitivity to MTX in JeG-3R choriocarcinoma cells. Increasing MTX sensitivity spears to be related to DNA damage induction by increased reactive oxygen species (ROS), apoptosis, and cell cycle arrest.CONCLUSIONS:
Data show that AKR1C3 is critical to the development of methotrexate resistance in choriocarcinoma and suggest that AKR1C3 may potentially serve as a therapeutic marker for this disease.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Coriocarcinoma
/
Hidroxiprostaglandina Desidrogenases
/
Metotrexato
/
Resistencia a Medicamentos Antineoplásicos
/
3-Hidroxiesteroide Desidrogenases
Limite:
Humans
Idioma:
En
Revista:
Int J Med Sci
Ano de publicação:
2014
Tipo de documento:
Article