Zhou Fangfei, Lu Qingge, Kong Lingyu, Wang Sitong, Zhang Haixia, Zhao Meng, Hu Yue, Wu Fanwu, Wu Chenxi
Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China.
Department of Dermatology, Xiong'an Xuanwu Hospital, Xiong'an, China.
Front Pharmacol. 2025 Jun 27;16:1549920. doi: 10.3389/fphar.2025.1549920. eCollection 2025.
Cancer is a global public health crisis and the leading cause of death among middle-aged and older individuals, with its incidence increasingly shifting toward younger populations. Approximately 90% of the patients succumb to advanced metastasis, and effective treatments remain elusive. The specific molecular mechanisms underlying cancer cell invasion and migration remain poorly understood, hindering the development of effective targeted therapies. Therefore, inhibiting or reversing cancer cell invasion and migration may be crucial for reducing mortality. Our previous research revealed that the five drugs (FD), derived from Xuefu Zhuyu Decoction (XFZYD), play a significant role in inhibiting cell migration.
HYPOTHESIS/PURPOSE: This study aims to explore the main drug components of FD and investigate the underlying mechanism in inhibiting cell migration.
We used the s cell migration model to investigate the effects of FD. FD was disassembled and analyzed using an orthogonal design. Drug extracts were prepared and administered to larvae. We assessed the effects of FD on cell migration, reactive oxygen species (ROS) levels, and gene expression.
In FD disassembled recipes and orthogonal test design, a significant difference was observed in the intervention with or without Fisch. (GUF) in migrating cell number ( < 0.01), which emerged as a more potent inhibitor of FD from XFZYD in cell migration. High-performance liquid chromatography revealed that GUF and its extract contained effective medicinal components, namely glycyrrhizic acid, liquiritin, liquiritigenin, and glycyrrhetinic acid. Moreover, GUF at 4.0 mg/mL displayed strong inhibitory effect in migrating cell number and distance when compared with model, XFZYD or FD. Excessive ROS can activate the JAK/STAT signaling pathway and promote the EMT process. GUF inhibited >induced cell migration by reducing ROS levels, JAK/STAT signalling, and the transcription of , , and . Finally, GUF rescued the altered expressions of the epithelial-mesenchymal transition (EMT)-related proteins, including matrix metalloproteinase 1 (MMP1), β-integrin and E-cadherin, triggered by cell migration.
Our findings demonstrate that GUF may serve as a promising candidate for targeting advanced metastatic tumors by suppressing ROS-mediated JAK/STAT signaling and EMT.
癌症是一场全球公共卫生危机，是中老年人群死亡的主要原因，其发病率正日益向年轻人群转移。约90%的患者死于晚期转移，有效的治疗方法仍然难以捉摸。癌细胞侵袭和迁移的具体分子机制仍知之甚少，这阻碍了有效靶向治疗的发展。因此，抑制或逆转癌细胞的侵袭和迁移对于降低死亡率可能至关重要。我们之前的研究表明，源自血府逐瘀汤（XFZYD）的五味药（FD）在抑制细胞迁移中发挥着重要作用。
假设/目的：本研究旨在探索FD的主要药物成分，并研究其抑制细胞迁移的潜在机制。
我们使用细胞迁移模型来研究FD的作用。采用正交设计对FD进行拆解和分析。制备药物提取物并施用于幼虫。我们评估了FD对细胞迁移、活性氧（ROS）水平和基因表达的影响。
在FD拆解配方和正交试验设计中，在有或没有 Fisch.（GUF）干预的迁移细胞数量上观察到显著差异（<0.01），GUF在XFZYD的FD中作为细胞迁移的更有效抑制剂出现。高效液相色谱显示GUF及其提取物含有有效药用成分，即甘草酸、甘草苷、甘草素和甘草次酸。此外，与模型、XFZYD或FD相比，4.0 mg/mL的GUF在迁移细胞数量和距离上显示出强烈的抑制作用。过量的ROS可激活JAK/STAT信号通路并促进EMT过程。GUF通过降低ROS水平、JAK/STAT信号传导以及 、 、 和 的转录来抑制>诱导的细胞迁移。最后，GUF挽救了由细胞迁移触发的上皮-间质转化（EMT）相关蛋白的表达改变，包括基质金属蛋白酶1（MMP1）、β-整合素和E-钙黏蛋白。
我们的研究结果表明，GUF可能通过抑制ROS介导的JAK/STAT信号传导和EMT成为靶向晚期转移性肿瘤的有希望的候选药物。
