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

doi:10.12122/j.issn.1673-4254.2026.02.03

Abstract

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

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.

Figures/Tables 15

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

References 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.