Beauvericin exerts an anti-tumor effect on hepatocellular carcinoma by inducing PI3K/AKT-mediated apoptosis

被引:2
作者
Wang, Gui [1 ]
Qiao, Yamei [1 ]
Zhao, Yunyan [1 ]
Song, Yuanyuan [1 ]
Li, Mengyang [1 ]
Jin, Min [1 ]
Yang, Dong [1 ]
Yin, Jing [1 ]
Li, Junwen [1 ,2 ]
Liu, Weili [1 ,2 ]
机构
[1] Tianjin Inst Environm & Operat Med, Tianjin 300050, Peoples R China
[2] Tianjin Inst Environm & Operat Med, 1 Dali Rd, Tianjin 300050, Peoples R China
基金
中国国家自然科学基金;
关键词
Beauvericin; PI3K/AKT pathway; Apoptosis; Hepatocellular carcinoma; ENNIATIN B; IN-VITRO; CANCER; CELL;
D O I
10.1016/j.abb.2023.109720
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Beauvericin is a world-spread mycotoxin isolated from the traditional Chinese medicine, Bombyx batryticatus (BB), which has been widely used to treat various neoplastic diseases. This study investigated the antihepatocellular carcinoma (HCC) activity of beauvericin and its potential mechanism. In this study, H22-bearing mice were intraperitoneally injected with 3, 5, 7 mg/kg of beauvericin once per-week over a threeweek period. TUNEL staining determined the extent of tumor apoptosis induced by beauvericin. ELISA kits detected the level of IL-2, Perforin, and TNF-& alpha;, IFN-& gamma; level in the serum. H22 hepatoma cells were exposed to beauvericin (5, 10, and 20 & mu;mol/L) to investigate the underlying pathway. CCK-8 assay was used to observe the influence of beauvericin on the growth of H22 cells. Flow cytometry was used to detect the cell apoptosis and ROS level. Western blotting was performed to detect apoptotic and PI3K/AKT pathway protein production. The results showed that beauvericin could remarkably inhibit the growth of HCC in mice, combined with elevated TNF-& alpha; and IL-2. In vitro, beauvericin significantly promoted the generation of ROS, up-regulated Bax/Bcl-2 ratio and cleaved caspase-9, cleaved caspase-3 levels, down-regulated p-PI3K/PI3K ratio, p-AKT/AKT ratio, promoted the apoptosis of H22 cells, and inhibited the growth of H22 cells. Remarkably, treatment with PI3K/AKT activator (740Y-P and SC79) could prevent beauvericin-induced H22 cell apoptosis. These findings collectively indicate that beauvericin inhibits HCC growth by inducing apoptosis via the PI3K/AKT pathway.
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页数:9
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