益气解毒方通过调控AKT1/GLUT1信号通路抑制鼻咽癌的恶性进展

doi:10.12122/j.issn.1673-4254.2026.02.03

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (2): 259-270.doi: 10.12122/j.issn.1673-4254.2026.02.03

• • 上一篇

益气解毒方通过调控AKT1/GLUT1信号通路抑制鼻咽癌的恶性进展

许红淼¹^,⁵(), 何兰²^,³, 熊雨¹^,³, 邹芳¹^,², 蔺婷³, 江志超³^,⁴, 唐乐¹^,³, 何迎春¹^,³(), 周芳亮¹^,³()

^1.湖南中医药大学，医学院，湖南长沙 410208
^2.湖南中医药大学，第一附属医院健康管理科，湖南长沙 410208
^3.湖南中医药大学，中医药防治眼耳鼻咽喉疾病湖南省重点实验室，湖南长沙 410208
^4.湖南省脑科医院中医科，湖南长沙 410021
^5.湖南省长沙市第四医院神经外科，湖南长沙 410219

收稿日期:2025-06-24 出版日期:2026-02-20 发布日期:2026-03-10
通讯作者: 何迎春,周芳亮 E-mail:125429219@qq.com;heyingchun@hnucm.edu.cn;zhoufangliang@hnucm.edu.cn
作者简介:许红淼，博士，副主任医师，E-mail: 125429219@qq.com
基金资助:
国家自然科学基金(82104941);国家自然科学基金(82305329);湖南省科技创新计划资助项目(2024RC3202);湖南省自然科学基金(2023JJ30449);湖南省卫生健康科研课题(20254150)

Yiqi Jiedu Formula inhibits proliferation, invasion and migration of nasopharyngeal carcinoma cells by inhibiting the AKT1/GLUT1 signaling pathway

Hongmiao XU¹^,⁵(), Lan HE²^,³, Yu XIONG¹^,³, Fang ZOU¹^,², Ting LIN³, Zhichao JIANG³^,⁴, Le TANG¹^,³, Yingchun HE¹^,³(), Fangliang ZHOU¹^,³()

^1.School of Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
^2.Department of Health Management of First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha 410208, China
^3.Hunan Provincial Key Lab for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
^4.Department of Traditional Chinese Medicine, Hunan Provincial Brain Hospital, Changsha 410021, China
^5.Department of Neurosurgery, Fourth Hospital of Changsha, Changsha 410219, China

Received:2025-06-24 Online:2026-02-20 Published:2026-03-10
Contact: Yingchun HE, Fangliang ZHOU E-mail:125429219@qq.com;heyingchun@hnucm.edu.cn;zhoufangliang@hnucm.edu.cn
Supported by:
National Natural Science Foundation of China(82104941)

摘要/Abstract

摘要：

目的研究AKT1/GLUT1信号通路在益气解毒方抗鼻咽癌中的作用。方法采用分子对接技术分析益气解毒方活性成分与AKT1的结合能力，MTT及RTCA法检测细胞增殖能力，划痕愈合实验检测细胞迁移能力，Matrigel侵袭小室法检测细胞侵袭能力，Western blotting法检测蛋白的表达变化。鼻咽癌裸鼠移植瘤模型分为对照组（等体积生理盐水灌胃）、益气组（以15.357 g·kg^-1·d^-1的益气解毒方灌胃）、5-Fu组（腹腔注射8 g·kg^-1·d^-1的5-氟尿嘧啶），10只/组，5-Fu组每2 d腹腔注射1次，其余2组灌胃1次/d，共给药18 d。结果与溶剂组比较，益气解毒方组细胞增殖速度、迁移和侵袭能力显著下降（P<0.05），p-AKT、GLUT1、XIAP、N-cadherin及Vimentin表达下调（P<0.05）；与单用益气解毒方组相比，GLUT1或AKT1激活剂与益气解毒方联用组细胞增殖速率提高，迁移和侵袭能力增强（P<0.05），XIAP、N-cadherin及Vimentin表达上调（P<0.05）；在鼻咽癌裸鼠移植瘤模型中，益气解毒方显著抑制肿瘤的生长并下调了肿瘤组织中AKT、p-AKT和GLUT1的表达（P<0.05）。结论益气解毒方抑制鼻咽癌细胞增殖、侵袭和迁移的机制与AKT1/GLUT1信号通路有关。

关键词: 鼻咽癌, 益气解毒方, AKT1/GLUT1, 侵袭与迁移

Abstract:

Objective To investigate the role of the AKT1/GLUT1 signaling pathway in mediating the inhibitory effect of Yiqi Jiedu Formula (YQJDF) against nasopharyngeal carcinoma (NPC) cells. Methods Molecular docking was employed to analyze the binding affinity between the active components of YQJDF and AKT1. MTT assay, real-time cell analysis (RTCA), wound healing assay and Matrigel invasion chamber assay were used to evaluate the effect of YQJDF extract on proliferation, migration and invasion abilities of human NPC cell lines 5-8F and 6-10B, and the changes in cellular protein expression levels were detected using Western blotting. In a BALB/c nude mouse model bearing NPC cell xenografts, tumor growth were observed following treatment with daily gavage with normal saline or YQJDF extract (15.357 g/kg) for 18 consecutive days or with intraperitoneal injections of 5-Fu every other day. The changes in the expressions of AKT1/GLUT1 signaling axis proteins in the xenografts were examined using Western blotting. Results In the NPC cell lines, treatment with YQJDF extract significantly inhibited cell proliferation, migration, and invasion, and downregulated the expressions of p-AKT, GLUT1, XIAP, N-cadherin, and vimentin. The application of GLUT1 or AKT1 activators partially reversed the inhibitory effects of YQJDF on the NPC cells. In the tumor-bearing mouse models, treatment with YQJDF extract obviously suppressed tumor growth and down-regulated the expression of AKT, p-AKT and GLUT1 in the tumor tissues. Conclusion YQJDF inhibits proliferation, invasion, and migration of NPC cells by inhibiting the AKT1/GLUT1 signaling pathway.

Key words: nasopharyngeal carcinoma, Yiqi Jiedu Formula, AKT1/GLUT1 signaling pathway, invasion and migration

许红淼, 何兰, 熊雨, 邹芳, 蔺婷, 江志超, 唐乐, 何迎春, 周芳亮. 益气解毒方通过调控AKT1/GLUT1信号通路抑制鼻咽癌的恶性进展[J]. 南方医科大学学报, 2026, 46(2): 259-270.

Hongmiao XU, Lan HE, Yu XIONG, Fang ZOU, Ting LIN, Zhichao JIANG, Le TANG, Yingchun HE, Fangliang ZHOU. Yiqi Jiedu Formula inhibits proliferation, invasion and migration of nasopharyngeal carcinoma cells by inhibiting the AKT1/GLUT1 signaling pathway[J]. Journal of Southern Medical University, 2026, 46(2): 259-270.

图/表 15

图1 益气解毒方对鼻咽癌细胞增殖的抑制作用

Fig.1 Inhibitory effect of Yiqi Jiedu Formula (YQ) on proliferation of nasopharyngeal carcinoma cells assessed using MTT assay (Mean±SD, n=5). **P<0.01 vs Solvent control group.

图2 益气解毒方入血成分与AKT1分子对接可视化图

Fig.2 Molecular docking between the blood components of Yiqi Jiedu Formula and AKT1.

图3 益气解毒方对鼻咽癌细胞6-10B AKT1/GLUT1信号通路的影响

Fig.3 Effect of Yiqi Jiedu Formula on the AKT1/GLUT1 signaling pathway in nasopharyngeal carcinoma 6-10B cells (n=3). *P<0.05, **P<0.01 vs Solvent control group.

图4 益气解毒方对鼻咽癌细胞5-8F AKT1/GLUT1信号通路的影响

Fig.4 Effect of Yiqi Jiedu Formula on the AKT1/GLUT1 signaling pathway in nasopharyngeal carcinoma 5-8F cells (n=3). *P<0.05, **P<0.01 vs Solvent control group.

图5 益气解毒方抑制鼻咽癌裸鼠移植瘤瘤体的增长

Fig.5 Yiqi Jiedu Formula inhibits growth of nasopharyngeal carcinoma cell xenografts in nude mice (n=10). *P<0.05, **P<0.01 vs Control group.

图6 益气解毒方对鼻咽癌5-8F细胞移植瘤组织AKT1/GLUT1信号轴的影响

Fig.6 Effect of Yiqi Jiedu Formula on AKT1/GLUT1 signaling axis in 5-8F cell xenografts in nude mice (n=3). *P<0.05, **P<0.01 vs Control group.

图7 激活AKT1对益气解毒方下调p-AKT1蛋白效应的影响

Fig.7 Effect of AKT1 activator on inhibitory effect of Yiqi Jiedu Formula on p-AKT1 protein in NPC cells (n=3). *P<0.05, **P<0.01 vs Solvent control group; #P<0.05, ##P<0.01 vs YQ group.

图8 激活GLUT1对益气解毒方下调GLUT1蛋白表达的影响

Fig.8 Effect of GLUT1 activator on inhibitory effect of Yiqi Jiedu Formula on GLUT1 protein in NPC cells (n=3). *P<0.05, **P<0.01 vs Solvent control group; #P<0.05 vs YQ group.

图9 激活AKT1对益气解毒方抑制鼻咽癌细胞增殖效应的影响

Fig.9 Effect of AKT1 activator on inhibitory effect of Yiqi Jiedu Formula on NPC cell proliferation (n=3). *P<0.05, **P<0.01 vs Solvent control group; #P<0.05, ##P<0.01 vs YQ group.

图10 GLUT1对益气解毒方抑制鼻咽癌细胞增殖效应的影响

Fig.10 Effect of GLUT1 activator on inhibitory effect of Yiqi Jiedu Formula on proliferation of NPC cells (n=3). *P<0.05, **P<0.01 vs Solvent control group; #P<0.05, ##P<0.01 vs YQ group.

图11 激活AKT1对益气解毒方抑制鼻咽癌细胞迁移效应的影响

Fig.11 Effect of AKT1 activator on inhibitory effect of Yiqi Jiedu Formula on NPC cell migration (Original magnification: ×40) (n=3). *P<0.05, **P<0.01 vs Solvent control group; #P<0.05, ##P<0.01 vs YQ group.

图12 GLUT1对益气解毒方抑制鼻咽癌细胞迁移效应的影响

Fig.12 Effect of GLUT1 activator on inhibitory effect of Yiqi Jiedu Formula on NPC cell migration (×40, n=3)). *P<0.05, **P<0.01 vs Solvent control group; #P<0.05, ##P<0.01 vs YQ group.

图13 GLUT1对益气解毒方抑制鼻咽癌细胞侵袭效应的影响

Fig.13 Effect of GLUT1 activator on inhibitoryeffect of Yiqi Jiedu Formula on NPC cellinvasion (×100, n=3). **P<0.01 vs Solventcontrol group; #P<0.05, ##P<0.01 vs YQ group.

图14 激活AKT1对益气解毒方抑制鼻咽癌细胞侵袭效应的影响

Fig.14 　Effect of AKT1 activator on inhibitoryeffect of Yiqi Jiedu Formula on NPC cellinvasion (×100, n=3). *P<0.05, **P<0.01 vsSolvent control group; ##P<0.01 vs YQ group.

图15 Western blotting检测激活AKT1/GLUT1信号通路对益气解毒方下调细胞增殖、EMT相关蛋白表达的影响

Fig.15 Effect of activating the AKT1/GLUT1 signaling pathway on inhibitory effects of Yiqi Jiedu Formula on NPC cell proliferation and EMT-related protein expressions detected by Western blotting (n=3). *P<0.05, **P<0.01 vs Solvent control group; #P<0.05, ##P<0.01 vs YQ group.

参考文献 31

[1]	Chen YP, Chan ATC, Le QT, et al. Nasopharyngeal carcinoma[J]. Lancet, 2019, 394(10192): 64-80. doi：10.1016/s0140-6736(19)30956-0
[2]	Wang Y, Chen Y, Liu Y, et al. Tumor vascular endothelial cells promote immune escape by upregulating PD-L1 expression via crosstalk between NF‑κB and STAT3 signaling pathways in nasopharyngeal carcinoma[J]. Cell Death Dis, 2025, 16(1): 129. doi：10.1038/s41419-025-07444-z
[3]	Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation[J]. Cell, 2011, 144(5): 646-74. doi：10.1016/j.cell.2011.02.013
[4]	Pavlova NN, Zhu JJ, Thompson CB. The hallmarks of cancer metabolism: still emerging[J]. Cell Metab, 2022, 34(3): 355-77. doi：10.1016/j.cmet.2022.01.007
[5]	Wang H, Hu J, Zhou W, et al. Metabolic reprogramming in the pathogenesis and progression of nasopharyngeal carcinoma: molecular mechanisms and therapeutic implications[J]. Am J Cancer Res, 2024, 14(8): 4049-64. doi：10.62347/vyat9271
[6]	Hu Y, Yu C, Cheng L, et al. Flavokawain C inhibits glucose metabolism and tumor angiogenesis in nasopharyngeal carcinoma by targeting the HSP90B1/STAT3/HK2 signaling axis[J]. Cancer Cell Int, 2024, 24(1): 158. doi：10.1186/s12935-024-03314-4
[7]	Fontana F, Giannitti G, Marchesi S, et al. The PI3K/Akt pathway and glucose metabolism: a dangerous liaison in cancer[J]. Int J Biol Sci, 2024, 20(8): 3113-25. doi：10.7150/ijbs.89942
[8]	王会杰, 孙珍贵, 赵文英, 等. S100A10可促进肺腺癌细胞的增殖和侵袭: 基于激活AktmTOR信号通路[J]. 南方医科大学学报, 2023, 43(5): 733-40.
[9]	Shao M, Pan QF, Tan HY, et al. CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer[J]. Genes Dis, 2024, 11(4): 101079. doi：10.1016/j.gendis.2023.101079
[10]	Wang CM, Li ZQ, Zhai HL, et al. Targeted blocking of EGFR and GLUT1 by compound H reveals a new strategy for treatment of triple-negative breast cancer and nasopharyngeal carcinoma[J]. Eur J Pharm Sci, 2024, 198: 106789. doi：10.1016/j.ejps.2024.106789
[11]	王贤文, 江志超, 唐发清, 等. 鼻咽癌“气虚染毒”病机的理论基础及其应用[J]. 中国中西医结合耳鼻咽喉科杂志, 2022,30(4):314-6，320.
[12]	覃琬婷, 王倩, 郑黎鹂, 等. 气化失常与肿瘤细胞能量代谢重编程[J]. 世界最新医学信息文摘, 2019, 19(92): 280, 282.
[13]	王大海, 田道法. 益气解毒颗粒配合放射治疗鼻咽癌的临床研究[J]. 湖南中医学院学报, 2006, 26(1): 36-7.
[14]	江志超, 田道法, 范靖莹. 益气解毒方对中晚期鼻咽癌患者CD4⁺CD25⁺调节性T细胞和Th17细胞的影响[J]. 中国中医药信息杂志, 2014, 21(2): 23-6, 31.
[15]	胡梅, 周芳亮, 宋岚, 等. 益气解毒颗粒协同顺铂对鼻咽癌移植瘤干预及调节Foxp3/ROR-γt平衡的作用[J]. 中草药, 2019, 50(9):2121-6.
[16]	何兰, 周芳亮, 邹攀, 等. 益气解毒方联合盐霉素通过CD44/Ras信号通路调控鼻咽癌干细胞增殖、迁移和凋亡（英文）[J]. DCM, 2020,3(4): 297-308.
[17]	周芳亮, 何兰, 何丹, 等. 益气解毒方水提物通过线粒体途径诱导鼻咽癌干细胞凋亡（英文）[J]. DCM, 2019, 2(4): 219-26.
[18]	蔺婷, 戴娜, 罗晶婧, 等. 益气解毒方通过PI3K/AKT/mTOR信号通路诱导鼻咽癌细胞自噬的研究[J]. 中华中医药杂志, 2020, 35(3):1484-8.
[19]	胡晶, 戴娜, 徐冰雁, 等. 益气解毒方通过MAPK/ERK信号通路抑制鼻咽癌细胞增殖[J]. 中国中药杂志, 2018, 43(6): 1221-7.
[20]	Zhou FL, Wang W, Xu RS, et al. Unraveling the mechanism of Yiqi Jiedu formula against nasopharyngeal carcinoma: an investigation integrating network pharmacology, serum pharmacochemistry, and metabolomics[J]. J Ethnopharmacol, 2024, 319: 117343. doi：10.1016/j.jep.2023.117343
[21]	You R, Liu YP, Xie YL, et al. Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial[J]. Lancet, 2023, 401(10380): 917-27. doi：10.1016/s0140-6736(23)00269-6
[22]	Chen X, Song Y, Tian Y, et al. miR-149-3p enhances drug sensitivity of AML cells by inhibiting Warburg effect through PI3K/AKT pathway[J]. Cell Biochem Biophys, 2024, 82(4): 3287-96. doi：10.1007/s12013-024-01412-8
[23]	Chen T, Xie S, Cheng J, et al. AKT1 phosphorylation of cytoplasmic ME2 induces a metabolic switch to glycolysis for tumorigenesis[J]. Nat Commun, 2024, 15(1): 686. doi：10.1038/s41467-024-44772-8
[24]	Pan C, Liu Q, Wu X. HIF1α/miR-520a-3p/AKT1/mTOR feedback promotes the proliferation and glycolysis of gastric cancer cells[J]. Cancer Manag Res, 2019, 11: 10145-56. doi：10.2147/cmar.s223473
[25]	Cai K, Chen S, Zhu C, et al. FOXD1 facilitates pancreatic cancer cell proliferation, invasion, and metastasis by regulating GLUT1-mediated aerobic glycolysis[J]. Cell Death Dis, 2022, 13(9): 765. doi：10.1038/s41419-022-05213-w
[26]	Dong S, Liang S, Cheng Z, et al. ROS/PI3K/Akt and Wnt/β-catenin signalings activate HIF-1α-induced metabolic reprogramming to impart 5-fluorouracil resistance in colorectal cancer[J]. J Exp Clin Cancer Res, 2022, 41(1): 15. doi：10.1186/s13046-021-02229-6
[27]	Loh CY, Chai JY, Tang TF, et al. The E-cadherin and N-cadherin switch in epithelial-to-mesenchymal transition: signaling, therapeutic implications, and challenges[J]. Cells, 2019, 8(10): E1118. doi：10.3390/cells8101118
[28]	Kawai M, Fukuda A, Ikeda M, et al. Polybromo 1/vimentin axis dictates tumor grade, epithelial-mesenchymal transition, and metastasis in pancreatic cancer[J]. J Clin Invest, 2025, 135(11): e177533. doi：10.1172/jci177533
[29]	陶露, 韦卓利, 王月月, 等. CEACAM6通过调控上皮间质转化抑制鼻咽癌细胞的增殖和迁移[J]. 南方医科大学学报, 2025,45(3):566-76.
[30]	Lu X, Zhang Y, Wang R, et al. Ginkgolide B inhibits EMT and promotes pyroptosis in gastric cancer via AKT/mTOR pathway[J]. Drug Des Devel Ther, 2025, 19: 2491-502. doi：10.2147/dddt.s485240
[31]	范婧莹, 刘洁, 蔺婷, 等. 益气解毒方通过Wnt/β-catenin信号通路诱导鼻咽癌5-8F细胞凋亡[J]. 中药新药与临床药理, 2022, 33(7):876-81.

益气解毒方通过调控AKT1/GLUT1信号通路抑制鼻咽癌的恶性进展

Yiqi Jiedu Formula inhibits proliferation, invasion and migration of nasopharyngeal carcinoma cells by inhibiting the AKT1/GLUT1 signaling pathway

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 15

参考文献 31

相关文章 15

编辑推荐

Metrics

本文评价

[1]	曾玉梅, 李继科, 黄仲曦, 周毅波. 绒毛样蛋白VILL通过与LMO7蛋白相互作用抑制鼻咽癌细胞的增殖[J]. 南方医科大学学报, 2025, 45(5): 954-961.
[2]	陶露, 韦卓利, 王月月, 项平. CEACAM6通过调控上皮间质转化抑制鼻咽癌细胞的增殖和迁移[J]. 南方医科大学学报, 2025, 45(3): 566-576.
[3]	刘瑨禹, 梁淑君, 张煜. 基于多尺度监督与残差反馈的优化算法有效提高鼻咽癌CT图像视交叉及视神经分割精度[J]. 南方医科大学学报, 2025, 45(3): 632-642.
[4]	李欣洋, 许桂晓, 刘洁宏, 冯衍秋. 人工智能辅助压缩感知加速技术对鼻咽癌MRI影像组学特征提取及分期诊断模型性能的影响[J]. 南方医科大学学报, 2025, 45(11): 2518-2526.
[5]	从小凡, 陈腾, 李硕, 王媛媛, 周龙云, 李小龙, 张配, 孙小锦, 赵素容. 双氢青蒿素通过促进活性氧的产生增强鼻咽癌细胞对顺铂诱导凋亡的敏感性[J]. 南方医科大学学报, 2024, 44(8): 1553-1560.
[6]	王媛媛, 陈腾, 从小凡, 李依然, 陈蕊, 张配, 孙小锦, 赵素容. 扁蒴藤素通过活性氧调控PI3K/AKT通路增强顺铂诱导鼻咽癌细胞凋亡[J]. 南方医科大学学报, 2024, 44(5): 904-912.
[7]	胡玥, 曾玉, 王琳婧, 廖志伟, 谭剑明, 邝燕好, 龚攀, 齐斌, 甄鑫. 多模态多分类器融合模型预测放射性口腔黏膜炎的性能[J]. 南方医科大学学报, 2024, 44(12): 2434-2442.
[8]	张浩轩, 陆进, 蒋成义, 方美芳. 基于人工智能技术的鼻咽癌风险预测模型的构建与评价[J]. 南方医科大学学报, 2023, 43(2): 271-279.
[9]	胡桐, 勾文峰, 任中昊, 刘改廷, 李祎亮, 左代英, 侯文彬. 淫羊藿素通过调控铁死亡增加鼻咽癌细胞的放射敏感性[J]. 南方医科大学学报, 2023, 43(10): 1665-1673.
[10]	张恒毅, 庞金龙, 张语涵, 马月, 范方田, 刘浩. AZD9291通过抑制PI3K-AKT-mTOR通路抑制鼻咽癌细胞的增殖和迁移[J]. 南方医科大学学报, 2022, 42(9): 1403-1409.
[11]	徐朦, 张鹏, 张国梁. 益气解毒方治疗原发性肝癌的作用机制：基于网络药理学及分子对接方法[J]. 南方医科大学学报, 2022, 42(6): 805-814.
[12]	周兰柱, 吴俊, 张明洁 , 赵报 , 马士崟. PRMT1通过促进RRM2表达抑制鼻咽癌细胞凋亡[J]. 南方医科大学学报, 2022, 42(12): 1783-1790.
[13]	高莉莉, 张雄, 窦思雨, 岳小丁, 杨捷玲. 干扰长链编码RNA FOXCUT能抑制鼻咽癌细胞上皮间质转化及诱导线粒体损伤[J]. 南方医科大学学报, 2021, 41(9): 1334-1341.
[14]	王文忠, 周兰柱, 孙哲, 吴俊, 崔忆旋. TRIM59靶向调控PPM1B对鼻咽癌侵袭和迁移的作用[J]. 南方医科大学学报, 2021, 41(7): 1030-1036.
[15]	陈星睿, 李登科, 黄仲曦, 钟水生, 蔡林波. EBV 阳性人鼻咽癌细胞外泌体促进淋巴管新生与鼻咽癌淋巴结转移[J]. 南方医科大学学报, 2020, 40(12): 1776-1783.