Uncovering the molecular mechanisms of Qingdu Zengye Decoction in the treatment of nasopharyngeal carcinoma: an integrative investigation
BackgroundNasopharyngeal 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 elucidatio...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1648294/full |
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| author | Qi Quan Qi Quan Zeyu Liu Zeyu Liu Ran Ding Yongmiao Lin Sihe Zhang Wei Luo Mengjie Lei Teng Fan Teng Fan Xin Su Xin Su Yuanyuan Huang Yuanyuan Huang Roujun Peng Bei Zhang Bei Zhang |
| author_facet | Qi Quan Qi Quan Zeyu Liu Zeyu Liu Ran Ding Yongmiao Lin Sihe Zhang Wei Luo Mengjie Lei Teng Fan Teng Fan Xin Su Xin Su Yuanyuan Huang Yuanyuan Huang Roujun Peng Bei Zhang Bei Zhang |
| author_sort | Qi Quan |
| collection | DOAJ |
| description | BackgroundNasopharyngeal 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.PurposeThis 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.MethodsAn 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.ResultsQZD 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.ConclusionQZD 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. |
| format | Article |
| id | doaj-art-6cf77c6ca6ec4c238f726d19a6fa8110 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-6cf77c6ca6ec4c238f726d19a6fa81102025-08-20T02:39:45ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16482941648294Uncovering the molecular mechanisms of Qingdu Zengye Decoction in the treatment of nasopharyngeal carcinoma: an integrative investigationQi Quan0Qi Quan1Zeyu Liu2Zeyu Liu3Ran Ding4Yongmiao Lin5Sihe Zhang6Wei Luo7Mengjie Lei8Teng Fan9Teng Fan10Xin Su11Xin Su12Yuanyuan Huang13Yuanyuan Huang14Roujun Peng15Bei Zhang16Bei Zhang17State 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, ChinaIntegrated Traditional Chinese and Western Medicine Research Center, Guangzhou, ChinaState 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, ChinaIntegrated Traditional Chinese and Western Medicine Research Center, Guangzhou, ChinaState 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, ChinaState 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, ChinaDepartment of Cell Biology, School of Medicine, Nankai University, Tianjin, ChinaState 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, ChinaInstitute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, ChinaState 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, ChinaIntegrated Traditional Chinese and Western Medicine Research Center, Guangzhou, ChinaState 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, ChinaIntegrated Traditional Chinese and Western Medicine Research Center, Guangzhou, ChinaState 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, ChinaIntegrated Traditional Chinese and Western Medicine Research Center, Guangzhou, ChinaState 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, ChinaState 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, ChinaIntegrated Traditional Chinese and Western Medicine Research Center, Guangzhou, ChinaBackgroundNasopharyngeal 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.PurposeThis 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.MethodsAn 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.ResultsQZD 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.ConclusionQZD 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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1648294/fullnasopharyngeal carcinomaQingdu Zengye Decoctionmolecular networksChinese herb medicinetherapeutic mechanism |
| spellingShingle | Qi Quan Qi Quan Zeyu Liu Zeyu Liu Ran Ding Yongmiao Lin Sihe Zhang Wei Luo Mengjie Lei Teng Fan Teng Fan Xin Su Xin Su Yuanyuan Huang Yuanyuan Huang Roujun Peng Bei Zhang Bei Zhang Uncovering the molecular mechanisms of Qingdu Zengye Decoction in the treatment of nasopharyngeal carcinoma: an integrative investigation Frontiers in Pharmacology nasopharyngeal carcinoma Qingdu Zengye Decoction molecular networks Chinese herb medicine therapeutic mechanism |
| title | Uncovering the molecular mechanisms of Qingdu Zengye Decoction in the treatment of nasopharyngeal carcinoma: an integrative investigation |
| title_full | Uncovering the molecular mechanisms of Qingdu Zengye Decoction in the treatment of nasopharyngeal carcinoma: an integrative investigation |
| title_fullStr | Uncovering the molecular mechanisms of Qingdu Zengye Decoction in the treatment of nasopharyngeal carcinoma: an integrative investigation |
| title_full_unstemmed | Uncovering the molecular mechanisms of Qingdu Zengye Decoction in the treatment of nasopharyngeal carcinoma: an integrative investigation |
| title_short | Uncovering the molecular mechanisms of Qingdu Zengye Decoction in the treatment of nasopharyngeal carcinoma: an integrative investigation |
| title_sort | uncovering the molecular mechanisms of qingdu zengye decoction in the treatment of nasopharyngeal carcinoma an integrative investigation |
| topic | nasopharyngeal carcinoma Qingdu Zengye Decoction molecular networks Chinese herb medicine therapeutic mechanism |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1648294/full |
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