Quan Qi, Liu Zeyu, Ding Ran, Lin Yongmiao, Zhang Sihe, Luo Wei, Lei Mengjie, Fan Teng, Su Xin, Huang Yuanyuan, Peng Roujun, Zhang Bei
State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Integrated Traditional Chinese and Western Medicine Research Center, Guangzhou, China.
Front Pharmacol. 2025 Jul 17;16:1648294. doi: 10.3389/fphar.2025.1648294. eCollection 2025.
Nasopharyngeal carcinoma (NPC) remains a therapeutic challenge due to its aggressive nature and limited treatment efficacy. Traditional Chinese Medicine, particularly Qingdu Zengye Decoction (QZD), has shown clinical potential, but its mechanistic basis in NPC treatment requires elucidation.
This study aims to elucidate the mechanisms of action of QZD in the treatment of NPC, focusing on its multi-target regulatory effects on cell apoptosis, oncogenic signaling pathways, and tumor immune microenvironment.
An integrative approach combining computational pharmacology, functional experiments, and single-cell transcriptomic profiling was employed to dissect QZD's anti-NPC mechanisms. Network pharmacology and protein-protein interaction (PPI) analysis was used to identify potential QZD targets. Functional assays (cell proliferation, apoptosis, colony formation) and Western blotting were used to validate key pathways. Molecular docking was applied to assessed ligand-target binding affinities. Single-cell RNA sequencing (scRNA-seq) was used to analyzed spatial expression patterns in NPC tumor samples.
QZD suppressed tumor progression by inducing apoptosis through modulating Bax in a dose-dependent manner and inhibiting the PI3K-Akt signaling pathway. Network pharmacology analysis identified AKT1, MTOR, HIF1A, SRC, and ESR1 as core regulatory genes. scRNA-seq revealed compartment-specific target localization: AKT1/ESR1 in tumor cells, SRC/IL6 in myeloid cells, and MTOR/HIF1A across stromal compartments. Molecular docking confirmed strong interactions between QZD compounds (e.g., quercetin, luteolin) and these targets. Upregulation of IL6 was observed and its dual immune-modulatory effects involving tumor suppression and microenvironment reprogramming was suggested.
QZD exerts anti-tumor effects in NPC through apoptosis induction, PI3K-Akt pathway suppression, and multi-compartmental tumor microenvironment modulation. Its ability to concurrently target oncogenic signaling and immune regulation positions QZD as a promising therapeutic strategy for advanced NPC.
鼻咽癌（NPC）因其侵袭性本质和有限的治疗效果，仍然是一个治疗挑战。传统中药，特别是清毒增液汤（QZD），已显示出临床潜力，但其在鼻咽癌治疗中的作用机制需要阐明。
本研究旨在阐明QZD治疗鼻咽癌的作用机制，重点关注其对细胞凋亡、致癌信号通路和肿瘤免疫微环境的多靶点调节作用。
采用计算药理学、功能实验和单细胞转录组分析相结合的综合方法，剖析QZD的抗鼻咽癌机制。利用网络药理学和蛋白质-蛋白质相互作用（PPI）分析来识别潜在的QZD靶点。功能测定（细胞增殖、凋亡、集落形成）和蛋白质印迹法用于验证关键通路。应用分子对接评估配体-靶点结合亲和力。单细胞RNA测序（scRNA-seq）用于分析鼻咽癌肿瘤样本中的空间表达模式。
QZD通过以剂量依赖方式调节Bax诱导细胞凋亡并抑制PI3K-Akt信号通路来抑制肿瘤进展。网络药理学分析确定AKT1、MTOR、HIF1A、SRC和ESR1为核心调控基因。scRNA-seq揭示了特定区域的靶点定位：肿瘤细胞中的AKT1/ESR1、髓样细胞中的SRC/IL6以及跨基质区域的MTOR/HIF1A。分子对接证实了QZD化合物（如槲皮素、木犀草素）与这些靶点之间有强烈的相互作用。观察到IL6上调，并提示其具有涉及肿瘤抑制和微环境重编程的双重免疫调节作用。
QZD通过诱导细胞凋亡、抑制PI3K-Akt通路和多区域肿瘤微环境调节在鼻咽癌中发挥抗肿瘤作用。其同时靶向致癌信号和免疫调节的能力使QZD成为晚期鼻咽癌的一种有前景的治疗策略。
