Screening of natural small molecule IDO-1 inhibitors with anti-tumor role / 药学学报
Acta Pharmaceutica Sinica
; (12): 1416-1423, 2017.
Article
en Zh
| WPRIM
| ID: wpr-779743
Biblioteca responsable:
WPRO
ABSTRACT
Fragments of the human indoleamine 2,3-dioxygenase 1 (IDO1) gene 5'-UTR (untranslated 1 245 bp region) promoters were amplified by PCR and cloned into pGL4.20 vector in the construction of reporter vector pGL4-IDO1-luc. A549 cells were transfected with the constructed plasmid and IDO1 inhibitor screening model was established with dual-luciferase reporter assay. Based on the model, we screened natural small molecules which could down-regulate the expression of IDO1 on tumor cells. The anti-tumor activities were examined by MTT, Western blotting and lactic dehydrogenase (LDH) release assays. Toosendanin (NS-180) down regulated the IDO1 expression and inhibited IFN-γ-induced STAT1 and STAT3 phosphorylation in A549 cells. Moreover, NS-180 significantly increased the cytotoxicity of co-cultured NK cells on A549 cells in LDH release assays. In summary, NS-180 is a novel and potent IDO1 inhibitor, which has an antitumor activity for cancer immunotherapies.
Texto completo:
1
Índice:
WPRIM
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Año:
2017
Tipo del documento:
Article