Elevated SRC3 expression predicts pemetrexed resistance in lung adenocarcinoma.
Biomed Pharmacother
; 125: 109958, 2020 May.
Article
en En
| MEDLINE
| ID: mdl-32036219
ABSTRACT
Lung cancer has been the leading cause of cancer-related death for many years worldwide. Pemetrexed, either as monotherapy or combined with other agents, is the preferred chemotherapy regimen for lung adenocarcinoma. However, both de novo and acquired resistance against pemetrexed frequently occur and lead to poor prognosis of patients. The underlying mechanisms remain poorly characterized. Here, RNA-seq analysis is utilized to compare gene expression levels in an adenocarcinoma cell line A549 with those in its pemetrexed-resistant counterpart, A549/PEM. We show that SRC3 is one of the most significantly upregulated genes in pemetrexed-resistant cells. SRC3 specifically enhances pemetrexed resistance in cultured adenocarcinoma cells. In addition, SRC3 increases pemetrexed resistance by decreasing chemotherapy-induced apoptosis via downregulating ROS level. Mechanistically, SRC3 enhances pemetrexed resistance via regulating Nrf2 and AKT signaling pathway. High SRC3 expression is positively correlated with decreased responsiveness to pemetrexed rather than other chemotherapeutic agents and predicts a poorer clinical outcome in lung adenocarcinoma patients. These data indicate that knockdown of SRC3 may be useful to treat pemetrexed-resistant lung cancer and may also provide a specific biomarker to predict pemetrexed responsiveness in lung cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Adenocarcinoma
/
Resistencia a Antineoplásicos
/
Coactivador 3 de Receptor Nuclear
/
Pemetrexed
/
Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2020
Tipo del documento:
Article
País de afiliación:
China