Screening of natural small molecule IDO-1 inhibitors with anti-tumor role
- VernacularTitle:IDO1天然小分子抑制剂的筛选及抗肿瘤作用研究
- Author:
Wei-qiang PANG
1
;
Lei GAO
2
;
Yue-ying DOU
1
;
Lu LIU
1
;
Na ZHANG
1
;
Xiao-jia LIU
1
;
Yang LIU
1
;
Zhao-yong YANG
1
;
Dan-qing SONG
1
;
Hong-bin DENG
1
Author Information
- Publication Type:ORIGINAL ARTICLES
- Keywords: indoleamine 2, 3-dioxygenase 1; promoter; luciferase; toosendanin
- From: Acta Pharmaceutica Sinica 2017;52(9):1416-1423
- CountryChina
- Language:Chinese
- 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.
