Chlorogenic acid down-regulates the expression of PD-L1 in esophageal squamous cell carcinoma via IFN-γ signaling pathway
10.16438/j.0513-4870.2021-0111
- VernacularTitle:绿原酸通过IFN-γ信号通路抑制食管癌细胞中PD-L1的表达
- Author:
Yun ZHAN
;
Rui LI
;
Xiao-lin LI
;
Yan-xing HAN
;
Jian-dong JIANG
- Publication Type:Research Article
- Keywords:
chlorogenic acid;
interferon-γ;
esophageal squamous cell carcinoma;
programmed cell death ligand 1;
interferon regulatory factor 1
- From:
Acta Pharmaceutica Sinica
2021;56(6):1599-1605
- CountryChina
- Language:Chinese
-
Abstract:
In this study, the regulatory effects of chlorogenic acid (CGA) on the expression of programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC), as well as the role of interferon γ (IFN-γ), has been discussed using both in vitro and in vivo animal models. ESCC murine model was established according to the standard operating procedures (SOP) of Animal Experiment Center of Institute of Materia Medica, Chinese Academy of Medical Sciences. The expression of PD-L1 in esophageal tissues of murine models was analyzed using the microarray assay. Then, the results were verified by qRT-PCR, Western blot and immunohistochemistry (IHC) staining, the molecular mechanism was explored in KYSE180 and KYSE510 ESCC cells in vitro. The results showed that CGA could suppress the expression of PD-L1 in tumor tissues in murine models significantly, rather than the expression in KYSE180 and KYSE510 ESCC cells in vitro. However, after the pretreatment of IFN-γ, the expression of PD-L1 was significantly increased, then it was down-regulated by CGA in both dose- and time-dependent manner. Meanwhile, the expression of interferon regulatory factor 1 (IRF1), an upstream regulatory factor of PD-L1, was suppressed by CGA in both KYSE180 and KYSE510 pretreated with IFN-γ, which was consistent with the expression of PD-L1. These results indicate that CGA down-regulates the expression of PD-L1 in ESCC via IFN-γ-IRF1 signaling pathway, providing the molecular theoretical basis for exploration of new treatment of ESCC.
