胡奇方通过调节PI3K/AKT/mTOR信号通路和促进T细胞浸润来抑制肝细胞癌的生长。

Huqi formula suppresses hepatocellular carcinoma growth by modulating the PI3K/AKT/mTOR pathway and promoting T cell infiltration.

作者信息

Yin Donghao, Li Xiang, Yang Xuemeng, Shang Xiaofei, Li Zhen, Geng Jiahao, Xu Yanyu, Xu Zijing, Wang Zixuan, Shang Zimeng, Yang Zhiyun, Hu Linlan, Li Quanwei, Wang Jiabo, Song Xinhua, Li Xiuhui, Wang Xiaojun

机构信息

Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.

Department of Natural Medicines, School of Traditional Chinese Medicine, Laboratory for Clinical Medicine, Capital Medical University, Beijing, 100069, China.

出版信息

Chin Med. 2025 Feb 19;20(1):25. doi: 10.1186/s13020-025-01061-w.

DOI:10.1186/s13020-025-01061-w

PMID:39972480

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11837637/

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) poses ongoing difficulties for public health systems due to its high incidence and poor prognosis. Huqi formula (HQF), a well-known prescription in traditional Chinese medicine, has demonstrated notable clinical effectiveness in the treatment of HCC. However, the mechanisms underlying its therapeutic effects have yet to be completely elucidated.

PURPOSE

This study aimed to investigate the anti-HCC effects of HQF and its underlying mechanisms.

METHODS

Chemical profiling and quantification of HQF were conducted by LC-MS and HPLC. Orthotopic and subcutaneous tumor models were established through hydrodynamic injection of Akt/Nras plasmids and subcutaneous injection of c-Met/sgPten cells, respectively, to evaluate the therapeutic effects of HQF on HCC. Network pharmacology, RNA-Seq, molecular docking, Western blot, and flow cytometry were employed to assess the anti-HCC mechanisms.

RESULTS

LC-MS analysis identified 41 components, with HPLC quantification showing salvianolic acid B as the most abundant compound (0.303%). In Akt/Nras and c-Met/sgPten-induced HCC models, HQF significantly reduced tissue damage, improved liver function, and inhibited HCC progression. Mechanistic studies revealed that HQF induced apoptosis in HCC cells by downregulating p-PI3K, p-AKT, and p-mTOR expression, with molecular docking indicating the strongest binding affinity between salvianolic acid B and PI3K. HQF further enhanced CD4 and CD8 T cell infiltration within the tumor microenvironment. When combined with PD-1 therapy, HQF improved therapeutic efficacy against HCC. Finally, toxicity assays confirmed the safety profile of HQF.

CONCLUSION

HQF demonstrated significant anti-HCC effects and a synergistic effect with PD-1, could be used as an alternative therapeutic agent for HCC.

摘要

背景

肝细胞癌（HCC）因其高发病率和预后不良，给公共卫生系统带来持续挑战。胡奇方（HQF）是一种著名的中药方剂，在HCC治疗中已显示出显著的临床疗效。然而，其治疗作用的潜在机制尚未完全阐明。

目的

本研究旨在探讨HQF的抗HCC作用及其潜在机制。

方法

通过液相色谱-质谱联用（LC-MS）和高效液相色谱（HPLC）对HQF进行化学图谱分析和定量。分别通过尾静脉注射Akt/Nras质粒和皮下注射c-Met/sgPten细胞建立原位和皮下肿瘤模型，以评估HQF对HCC的治疗效果。采用网络药理学、RNA测序、分子对接、蛋白质免疫印迹法和流式细胞术评估抗HCC机制。

结果

LC-MS分析鉴定出41种成分，HPLC定量显示丹酚酸B是含量最高的化合物（0.303%）。在Akt/Nras和c-Met/sgPten诱导的HCC模型中，HQF显著减轻组织损伤，改善肝功能，并抑制HCC进展。机制研究表明，HQF通过下调p-PI3K、p-AKT和p-mTOR表达诱导HCC细胞凋亡，分子对接表明丹酚酸B与PI3K之间的结合亲和力最强。HQF进一步增强了肿瘤微环境中CD4和CD8 T细胞的浸润。当与PD-1治疗联合使用时，HQF提高了对HCC的治疗效果。最后，毒性试验证实了HQF的安全性。