Inhibition of XPO1 impairs cholangiocarcinoma cell proliferation by triggering p53 intranuclear accumulation.
Cancer Med
; 12(5): 5751-5763, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36200270
ABSTRACT
BACKGROUND:
XPO1 mediates the nuclear export of several proteins, mainly tumor suppressors. KPT-330 (Selinexor) is a selective inhibitor of XPO1 that has demonstrated good therapeutic effects in hematologic cancers.METHODS:
We used TCGA and GTEx pan-cancer database to evaluate XPO1 mRNA expression in various tumors. Cell proliferation assay and colony formation assay were used to analyze the in vitro antitumor effects of XPO1 inhibitor KPT-330. Western blot was performed to explore the specific mechanisms.RESULTS:
We found that XPO1 was highly expressed across a range of cancers and associated with poor prognosis in hepatobiliary and pancreatic tumors. We revealed that the XPO1 inhibitor KPT-330 triggered the nuclear accumulation of the p53 protein and significantly disrupted the proliferation of cholangiocarcinoma cells. Mechanistically, the XPO1 inhibitor, KPT-330, reduced BIRC6 expression by inhibiting the PI3K/AKT pathway to decrease p53 degradation and improve its stability.CONCLUSION:
Therefore, XPO1 may be a potential therapeutic target in cholangiocarcinoma, mediated by its effects on KPT-330.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colangiocarcinoma
/
Carioferinas
Limite:
Humans
Idioma:
En
Revista:
Cancer Med
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China