Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, China.
Department of VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Curr Pharm Des. 2024;30(24):1894-1911. doi: 10.2174/0113816128287535240429043610.
Huaier ( Murr), a traditional Chinese medicine, is widely used in China as a complementary and alternative therapy to treat hepatocellular carcinoma (HCC). Past studies have shown that Huaier can arrest the cell cycle, promote apoptosis and inhibit the proliferation of cancer cells. However, how it regulates the metabolism of HCC is still unclear.
This study explores the metabolic-related function of Huaier in treating HCC with an in-silico approach.
A network pharmacology and bioinformatics-based approach was employed to investigate the molecular pathogenesis of metabolic reprogramming in HCC with Huaier. The compounds of Huaier were obtained from public databases. Oral bioavailability and drug likeness were screened using the TCMSP platform. The differential gene expressions between HCC and non-tumor tissue were calculated and used to find the overlap from the targets of Huaier. The enrichment analysis of the overlapped targets by Metascape helped filter out the metabolism-related targets of Huaier in treating HCC. Protein-protein interaction (PPI) network construction and topological screening revealed the hub nodes. The prognosis and clinical correlation of these targets were validated from the cancer genome atlas (TCGA) database, and the interactions between the hub nodes and active ingredients were validated by molecular docking.
The results showed that Peroxyergosterol, Daucosterol, and Kaempferol were the primary active compounds of Huaier involved in the metabolic reprogramming of HCC. The top 6 metabolic targets included AKR1C3, CYP1A1, CYP3A4, CYP1A2, CYP17A1, and HSD11B1. The decreased expression of CYP3A4 and increased expression of AKR1C3 were related to the poor overall survival of HCC patients. The molecular docking validated that Peroxyergosterol and Kaempferol exhibited the potential to modulate CYP3A4 and AKR1C3 from a computational perspective.
This study provided a workflow for understanding the mechanism of Huaier in regulating the metabolic reprogramming of HCC.
槐耳（Murr）是一种传统中药，在中国被广泛用作治疗肝细胞癌（HCC）的辅助和替代疗法。过去的研究表明，槐耳可以阻止细胞周期，促进细胞凋亡并抑制癌细胞的增殖。但是，它如何调节 HCC 的代谢仍不清楚。
本研究采用计算机模拟方法探讨槐耳治疗 HCC 的代谢相关功能。
采用网络药理学和生物信息学方法，研究槐耳治疗 HCC 时代谢重编程的分子发病机制。从公共数据库中获取槐耳的化合物。使用 TCMSP 平台筛选口服生物利用度和药物相似性。计算 HCC 与非肿瘤组织之间的差异基因表达，并从槐耳的靶标中寻找重叠。Metascape 对重叠靶标进行富集分析有助于筛选槐耳治疗 HCC 中的代谢相关靶标。蛋白质-蛋白质相互作用（PPI）网络构建和拓扑筛选揭示了枢纽节点。从癌症基因组图谱（TCGA）数据库中验证这些靶标的预后和临床相关性，并通过分子对接验证枢纽节点和活性成分之间的相互作用。
结果表明，过氧化麦角甾醇、豆甾醇和山奈酚是槐耳参与 HCC 代谢重编程的主要活性成分。前 6 个代谢靶标包括 AKR1C3、CYP1A1、CYP3A4、CYP1A2、CYP17A1 和 HSD11B1。CYP3A4 表达降低和 AKR1C3 表达增加与 HCC 患者总体生存率差相关。分子对接验证了从计算角度来看，过氧化麦角甾醇和山奈酚具有调节 CYP3A4 和 AKR1C3 的潜力。
本研究为理解槐耳调节 HCC 代谢重编程的机制提供了一种工作流程。
