He Yongfei, Tao Qiang, Mo Shutian, Chen Meifeng, Wang Jicai, Zhai Hang, Hong Shengjie, Gao Qiang, Zhang Guangquan, Han Chuangye, Shi Xianjie
Department of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Front Oncol. 2025 Jul 30;15:1523570. doi: 10.3389/fonc.2025.1523570. eCollection 2025.
Hepatocellular carcinoma (HCC) is a common tumor that endangers health. Depression will affect the therapeutic effect of HCC, and depression and HCC promote and influence each other. Ansofaxine Hydrochloride is a novel antidepressant, and its anti-HCC effect remains to be confirmed.
This study aimed to investigate the effect of Ansofaxine Hydrochloride on HCC and its molecular mechanism.
The potential targets and signaling pathways of Ansofaxine Hydrochloride against HCC were obtained by network pharmacology, and the key targets were explored by molecular docking techniques. Hepatocellular carcinoma cells were treated with different concentrations of Ansofaxine Hydrochloride, and the effects of Ansofaxine Hydrochloride on the biological function of hepatocellular carcinoma cells were evaluated by CCK8, migration, invasion, and clonal formation tests. Subsequently, a subcutaneous hepatocellular carcinoma mouse model was established to evaluate the effect of Ansofaxine Hydrochloride on the growth of hepatocellular carcinoma tissue , and an enzym-linked immunosorbent assay was used to detect the levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) in peripheral blood. HE and immunohistochemical staining were used to detect the pathological changes of tumor tissue and the types and proportions of macrophages. Finally, the expression levels of key genes in the EGFR/MAPK pathway were detected by Reverse Transcription Real-time Quantitative analysis.
There are 87 common drug-disease targets between Ansofaxine Hydrochloride and HCC, including EGFR, GRB2, and SRC, which are mainly involved in EGFR, MAPK, and PI3K/AKT signaling pathways. Molecular docking showed that Ansofaxine Hydrochloride has good binding activity to EGFR, GRB2, and other key targets. experiments showed that Ansofaxine Hydrochloride has significant inhibitory effects on proliferation, migration, invasion, and clonal formation of HCC cells. experiments showed that Ansofaxine Hydrochloride has a synergistic effect of enhancingLenvatinib anti-HCC, enhancing peripheral blood DA level, promoting M1 macrophage infiltration, and enhancing immune anti-tumor effects, and is associated with the reduction of EGFR/MAPK pathway-related genes.
Our study suggests that Ansofaxine Hydrochloride has anti-HCC and immunomodulatory effects, with the EGFR/MAPK pathway as a potential key mechanism of action.
肝细胞癌（HCC）是一种常见的危害健康的肿瘤。抑郁症会影响HCC的治疗效果，且抑郁症与HCC相互促进、相互影响。盐酸安索法辛是一种新型抗抑郁药，其抗HCC作用尚待证实。
本研究旨在探讨盐酸安索法辛对HCC的作用及其分子机制。
通过网络药理学获得盐酸安索法辛抗HCC的潜在靶点和信号通路，并通过分子对接技术探索关键靶点。用不同浓度的盐酸安索法辛处理肝癌细胞，通过CCK8、迁移、侵袭和克隆形成试验评估盐酸安索法辛对肝癌细胞生物学功能的影响。随后，建立皮下肝癌小鼠模型，评估盐酸安索法辛对肝癌组织生长的影响，并用酶联免疫吸附测定法检测外周血中多巴胺（DA）和5-羟色胺（5-HT）水平。采用HE和免疫组化染色检测肿瘤组织的病理变化以及巨噬细胞的类型和比例。最后，通过逆转录实时定量分析检测EGFR/MAPK通路中关键基因的表达水平。
盐酸安索法辛与HCC之间有87个共同的药物-疾病靶点，包括EGFR、GRB2和SRC，主要涉及EGFR、MAPK和PI3K/AKT信号通路。分子对接显示盐酸安索法辛对EGFR、GRB2等关键靶点具有良好的结合活性。实验表明盐酸安索法辛对HCC细胞的增殖、迁移、侵袭和克隆形成具有显著抑制作用。实验表明盐酸安索法辛具有增强仑伐替尼抗HCC的协同作用，提高外周血DA水平，促进M1巨噬细胞浸润，增强免疫抗肿瘤作用，并与EGFR/MAPK通路相关基因的减少有关。
我们的研究表明盐酸安索法辛具有抗HCC和免疫调节作用，EGFR/MAPK通路是其潜在的关键作用机制。
