Biochanin A Suppresses Tumor Progression and PD-L1 Expression via Inhibiting ZEB1 Expression in Colorectal Cancer

Junying Xu; Xuejing Yang; Jiadong Pan; Honghong Fan; Jie Mei; Dong Hua

doi:10.1155/2022/3224373

Biochanin A Suppresses Tumor Progression and PD-L1 Expression via Inhibiting ZEB1 Expression in Colorectal Cancer

J Oncol. 2022 Feb 22:2022:3224373. doi: 10.1155/2022/3224373. eCollection 2022.

Authors

Junying Xu¹, Xuejing Yang¹, Jiadong Pan², Honghong Fan¹, Jie Mei¹, Dong Hua¹

Affiliations

¹ Department of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, Jiangsu, China.
² Department of Gastroenterology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, Jiangsu, China.

Abstract

Objective: To investigate the regulatory effect of ZEB1 on PD-L1 expression and the pharmacodynamic effects of Biochanin A on the malignant biological behaviors of colorectal cancer (CRC).

Methods: The correlation between epithelial-mesenchymal transition (EMT) score and features of the tumor microenvironment (TME) was investigated using the Cancer Genome Atlas (TCGA) dataset. The correlation between ZEB1 and PD-L1 expression was validated using immunohistochemistry (IHC) staining, and the regulatory effect of ZEB1 on PD-L1 expression was explored by in vitro assays. Moreover, the pharmacodynamic effects of Biochanin A on ZEB1 and PD-L1 expression, as well as malignant biological behaviors of CRC cells, were evaluated by in vitro and in vivo assays.

Results: EMT score was positively correlated with a majority of immunostimulators, immune checkpoints, activities of antitumor immunity cycles, and infiltration levels of most immune cells in the TCGA dataset. In addition, ZEB1 was correlated with and positively regulated PD-L1 expression in CRC. Besides, Biochanin A, an inhibitor for the ZEB1/PD-L1 axis, notably inhibited ZEB1-mediated aggressiveness and PD-L1 expression of CRC cells. Moreover, Biochanin A also exerted a tumor-inhibitory role in vivo in the CRC mouse model.

Conclusion: Overall, we found that ZEB1 is a main regulator of PD-L1 expression in CRC. In addition, we also identified Biochanin A as a novel inhibitor for the ZEB1/PD-L1 axis, which could inhibit tumor progression and immune escape.