Screening novel inhibitors of squalene epoxidase and their effects on hepatocellular carcinoma
10.16438/j.0513-4870.2023-0788
- VernacularTitle:角鲨烯环氧化酶新型抑制剂的筛选及其抗肝癌的作用
- Author:
Liang-qi GUO
1
;
Ya-li LIU
1
;
Xiao TAN
1
;
Ting ZHAI
2
,
3
;
De-qiao SHENG
1
;
Ya-yun LIU
1
,
3
,
4
Author Information
1. Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China
2. Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National &
3. Local Joint Engineering Research Center of High Throughput Drug Screening Technology, Hubei University, Wuhan 430062, China
4. Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National &
- Publication Type:Research Article
- Keywords:
squalene epoxidase;
novel inhibitor;
liver cancer;
cholesterol;
proliferation;
migration
- From:
Acta Pharmaceutica Sinica
2023;58(9):2707-2714
- CountryChina
- Language:Chinese
-
Abstract:
Squalene epoxidase (SQLE) is a potential target for the treatment of liver cancer. Bioinformatics analysis indicated that the high expression of SQLE was closely related to the clinical stage and poor prognosis of patients with liver cancer. However, the existing inhibitors against SQLE 195 tyrosine residue (Y195) cannot be used clinically due to severe side effects. In this study, 35 small-molecule compounds targeting SQLE 335 tyrosine residue (Y335) were selected by computer virtual screening. Combined with MTT assay, 3 candidate compounds (19#, 31# and 35#) with significant inhibitory effects on the proliferation of Huh7 cell line were obtained. Further studies showed that these 3 compounds could inhibit the migration of Huh7 cells, reduce the contents of total and free cholesterol, up-regulate the expression of tumor suppressor gene PTEN, and down-regulate the expression of PI3K and AKT proteins. The results showed that the novel inhibitors 19#, 31# and 35# targeting SQLE Y335 could reduce cholesterol content, inhibit the proliferation and migration of Huh7, thus playing an anti-liver cancer role.
