cirsiliol通过调节谷氨酰胺代谢抑制肝细胞癌的恶性进展。
Cirsiliol suppresses malignant progression of hepatocellular carcinoma via regulation of glutamine metabolism.
作者信息
Zhang Bin, Zheng Jianbo, Zheng Siming
机构信息
Hepatopancreatobiliary Surgery Department, The First Affiliated Hospital of Ningbo University No. 59, Liuting Street, Haishu District, Ningbo 315000, Zhejiang, China.
出版信息
Am J Transl Res. 2025 Mar 15;17(3):2145-2153. doi: 10.62347/AOTY4308. eCollection 2025.
BACKGROUND
To investigate the therapeutic potential of cirsiliol in hepatocellular carcinoma (HCC), focusing on its impact on glutamine metabolism.
METHODS
HCC cell lines HCCLM3 and Huh7 were treated with cirsiliol, and cell viability and proliferation were assessed using CCK-8 assay. Intracellular concentrations of glutamine, α-ketoglutaric acid (α-KG), and adenosine triphosphate (ATP) were measured to evaluate glutamine metabolism. A xenograft tumor model was employed to examine the in vivo effects of cirsiliol. Additionally, network pharmacological analysis was used to identify potential targets of cirsiliol in HCC. Western blotting was conducted to analyze the modulation of the PI3K/AKT signaling pathway by cirsiliol.
RESULTS
Cirsiliol significantly inhibited HCC cell growth both in vitro and in vivo while reducing levels of glutamine, α-KG, and ATP, indicating suppression of glutamine metabolism. Activation of the PI3K signaling pathway reversed the inhibitory effects of cirsiliol on HCC cell growth and metabolism.
CONCLUSION
Cirsiliol suppresses glutamine metabolism and inhibits the growth of HCC cells by modulating the PI3K/AKT signaling pathway.
背景
研究cirsiliol对肝细胞癌（HCC）的治疗潜力，重点关注其对谷氨酰胺代谢的影响。
方法
用cirsiliol处理肝癌细胞系HCCLM3和Huh7，采用CCK-8法评估细胞活力和增殖。测量细胞内谷氨酰胺、α-酮戊二酸（α-KG）和三磷酸腺苷（ATP）的浓度以评估谷氨酰胺代谢。采用异种移植肿瘤模型研究cirsiliol的体内作用。此外，利用网络药理学分析确定cirsiliol在肝癌中的潜在靶点。进行蛋白质免疫印迹分析cirsiliol对PI3K/AKT信号通路的调节作用。
结果
cirsiliol在体外和体内均显著抑制肝癌细胞生长，同时降低谷氨酰胺、α-KG和ATP水平，表明其抑制谷氨酰胺代谢。PI3K信号通路的激活逆转了cirsiliol对肝癌细胞生长和代谢的抑制作用。
结论
cirsiliol通过调节PI3K/AKT信号通路抑制谷氨酰胺代谢并抑制肝癌细胞生长。
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