槲皮素通过调控Hippo通路蛋白YAP表达抑制胃癌细胞增殖与迁移并促进其凋亡

doi:10.12122/j.issn.1673-4254.2026.02.15

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (2): 374-384.doi: 10.12122/j.issn.1673-4254.2026.02.15

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槲皮素通过调控Hippo通路蛋白YAP表达抑制胃癌细胞增殖与迁移并促进其凋亡

王煜煌¹(), 王文锐²(), 程淑洁¹, 冯云龙¹, 张卓¹, 施其英¹, 李雨佳¹, 胡茜文¹, 吴明彩¹()

^1.皖南医学院生物化学与分子生物学教研室，安徽芜湖 241200
^2.安徽省肿瘤演进及智能诊疗重点实验室，安徽蚌埠 233000

收稿日期:2025-04-08 出版日期:2026-02-20 发布日期:2026-03-10
通讯作者: 吴明彩 E-mail:1723221321@qq.com;wenrui-wang1983@163.com;williyia@wnmc.edu.cn
作者简介:王煜煌，在读硕士研究生，E-mail: 1723221321@qq.com
王文锐，教授，E-mail: wenrui-wang1983@163.com
第一联系人：共同第一作者
基金资助:
癌症转化医学安徽省重点实验室开放课题(KFKT202303);中青年教师培养行动项目(JWFX2024027);国家级大学生创新创业训练计划项目(202310368011);安徽省大学生创新创业训练计划项目(S202310368031);安徽省大学生创新创业训练计划项目(S202410368040)

Quercetin inhibits proliferation and migration and promotes apoptosis of gastric cancer cells by promoting phosphorylation-mediated YAP inactivation

Yuhuang WANG¹(), Wenrui WANG²(), Shujie CHENG¹, Yunlong FENG¹, Zhuo ZHANG¹, Qiying SHI¹, Yujia LI¹, Qianwen HU¹, Mingcai WU¹()

^1.Department of Biochemistry and Molecular Biology, Wannan Medical College, Wuhu 241200, China
^2.Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical University, Bengbu 233000, China

Received:2025-04-08 Online:2026-02-20 Published:2026-03-10
Contact: Mingcai WU E-mail:1723221321@qq.com;wenrui-wang1983@163.com;williyia@wnmc.edu.cn

摘要/Abstract

摘要：

目的探索槲皮素调控胃癌细胞增殖、迁移与凋亡的分子机制。方法生物信息学分析Hippo通路蛋白YAP在胃癌和胃癌旁正常组织的表达差异和生存率。Western blotting检测各样本中YAP和磷酸化YAP（p-YAP）的表达水平。槲皮素处理胃癌细胞，CCK8检测细胞活力；敲低YAP基因和槲皮素处理胃癌细胞进行分析比较，EdU、集落形成实验检测细胞增殖，Transwell检测细胞迁移；流式细胞术检测细胞凋亡；Western blotting 和RT-qPCR检测相关基因和蛋白表达水平；免疫荧光检测蛋白定位。过表达YAP基因进行回复实验验证。结果 YAP在胃癌组织的表达显著高于癌旁正常组织（P<0.05）；YAP的表达与胃癌患者存活率呈负相关（P<0.01）；槲皮素可明显降低胃癌细胞的存活率（P<0.01），促进MST1和LATS1蛋白表达，激活Hippo信号通路，导致YAP的磷酸化失活，核转位减少（P<0.05）；敲降YAP表达和槲皮素处理均能够明显抑制胃癌细胞的增殖、迁移能力，促进细胞的凋亡（P<0.05）；过表达YAP能够明显降低槲皮素对胃癌细胞增殖、迁移能力的抑制作用和凋亡的促进作用（P<0.05）。结论槲皮素可促进YAP磷酸化降解抑制胃癌细胞的增殖和迁移，促进细胞凋亡。

关键词: 槲皮素, Hippo信号通路, 转录共激活相关蛋白, 磷酸化, 胃癌

Abstract:

Objective To explore the molecular mechanisms by which quercetin regulates proliferation, migration, and apoptosis of gastric cancer cells. Methods Bioinformatics analysis was conducted to examine the differential expression of Hippo pathway protein yes-associated protein (YAP) between gastric cancer and normal tissues and its correlation with patient survival rates. CCK-8 assay was used to evaluate the effect of quercetin on viability of gastric cancer HGC-27 cells. The expression levels of YAP and phosphorylated YAP (p-YAP) in gastric cancer and normal gastric tissues were detected using Western blotting. In HGC-27 cells with YAP knockdown, the effects of quercetin treatment on cell proliferation, migration and apoptosis were assessed using EdU assay, colony formation assay, Transwell assay, and flow cytometry; the localization of YAP was determined using immunofluorescence staining. Rescue experiments were performed by overexpressing YAP in HGC-27 cells. Results YAP expression was markedly lower in gastric cancer tissues than in normal tissues, and its expression level was negatively correlated with patient survival rates. Quercetin significantly inhibited the survival of HGC-27 cells, promoted MST1 and LATS1 expression, and activated the Hippo signaling pathway, leading to phosphorylation-mediated inactivation of YAP, thereby reducing its nuclear translocation. Both YAP knockdown and quercetin treatment significantly suppressed proliferation and migration and promoted apoptosis of HGC-27 cells. Overexpression of YAP substantially attenuated the inhibitory effects of quercetin in HGC-27 cells. Conclusion Quercetin inhibits proliferation and migration and promotes apoptosis of gastric cancer cells by promoting phosphorylation-mediated inactivation of YAP.

Key words: Quercetin, Hippo signaling pathway, yes-associated protein, phosphorylation, gastric cancer

王煜煌, 王文锐, 程淑洁, 冯云龙, 张卓, 施其英, 李雨佳, 胡茜文, 吴明彩. 槲皮素通过调控Hippo通路蛋白YAP表达抑制胃癌细胞增殖与迁移并促进其凋亡[J]. 南方医科大学学报, 2026, 46(2): 374-384.

Yuhuang WANG, Wenrui WANG, Shujie CHENG, Yunlong FENG, Zhuo ZHANG, Qiying SHI, Yujia LI, Qianwen HU, Mingcai WU. Quercetin inhibits proliferation and migration and promotes apoptosis of gastric cancer cells by promoting phosphorylation-mediated YAP inactivation[J]. Journal of Southern Medical University, 2026, 46(2): 374-384.

图/表 9

表1 LATS1、YAP、CYR61、CTGF和GAPDH引物序列

Tab.1 Primer sequences for RT-qPCR

Primer	Forward (5'-3')	Reverse (5'-3')
LATS1	GTCGACGAGAGCAGATGGC	CACTTTCTCCTAGTGGCGGG
YAP	TGACCCTCGTTTTGCCATGA	GTTGCTGCGGTTGGAGTTG
CYR61	CAGGACTGTGAAGATGCGT	AGCCTGTAGAAGGGAAACGC
CTGF	GTCGAGTATGTACCGACGCG	GCAGGCACAGGTCTTGATGA
GAPDH	CGAGCCACATCGCTCAGACA	GTGGTGAAGACGCCAGTGGA

图1 YAP在胃癌组织的表达水平及YAP表达在胃癌患者存活率的关系

Fig.1 Expression levels of YAP and p-YAP in gastric cancer (GC) tissues and the correlation of YAP expression level with patient survival. A： Expression of YAP in GC (T) tissues and normal tissues (N) analyzed using the TCGA database. B： Correlation of YAP expression level with patient survival. C, D： Expression of YAP and p-YAP protein in normal gastric tissues and GC tissues. *P<0.05, ***P<0.001 vs Normal tissues.

图2 敲降YAP表达对细胞增殖、迁移和凋亡的影响

Fig.2 Effects of YAP knockdown on cell proliferation, migration and apoptosis. A, B: YAP expression levels in HGC-27 cells with YAP knockdown. C: mRNA expression levels of YAP, CYR61 and CTGF in HGC-27 cells with YAP knockdown. D, E: EdU assays of HGC-27 cells with YAP knockdown （Scale bar=200 μm）. F, G: Colony formation assays of HGC-27 cells with YAP knockdown. H, I: Transwell migration assays of HGC-27 cells with YAP knockdown （Scale bar=100 μm）. J, K: Flow cytometric analysis of apoptosis of HGC-27 cells with YAP knockdown. *P<0.05, **P<0.01, ***P<0.001 vs si-NC group.

图3 槲皮素抑制胃癌细胞HGC-27的细胞活力

Fig.3 Quercetin inhibits viability of HGC-27 cells. **P<0.01, ***P<0.001 vs 0 μmol/L group.

图4 槲皮素对胃癌细胞的增殖的影响

Fig.4 Effects of quercetin on proliferation of HGC-27 cells. A, B:EdU assays for assessing proliferation of quercetin-treated HGC-27 cells (Scale bar=200 μm). C, D: Colony formation assays assessing proliferation of quercetin-treated HGC-27 cells. *P<0.05, **P<0.01 vs 0 μmol/L group.

图5 槲皮素对胃癌细胞迁移和凋亡的影响

Fig.5 Effects of quercetin on migration and apoptosis of HGC-27 cells. A, B: Transwell migration assays for assessing migratory ability of quercetin-treated HGC-27 cells (Scale bar=100 μm). C, D: Flow cytometry analysis of apoptosis of quercetin on quercetin-treated HGC-27 cells. *P<0.05, **P<0.01 vs 0 μmol/L group.

图6 槲皮素对Hippo信号通路蛋白的表达影响

Fig.6 Effect of quercetin on Hippo signaling pathway protein expression in HGC-27 cells. A, B: Effect of 0-50 μmol/L quercetin on MST1, LATS1 and YAP protein expressions in HGC-27 cells. C, D： Effects of 50 μmol/L quercetin treatment for 24 h on MST1, p-MST1 LATS1, p-LATS1, YAP and p-YAP expression. E: Effect of 50 μmol/L quercetin on mRNA expression of LATS1, YAP and its downstream target genes CYR61 and CTGF in HGC-27 cells. F: Immunofluorescence staining for analyzing YAP nuclear and cytoplasmic expression in 50 μmol/L quercetin-treated HGC-27 cells (Scale bar=20 μm).*P<0.05, **P<0.01 vs 0 μmol/L group. #P<0.05, ##P<0.01 vs 0 h group.

图7 过表达YAP对槲皮素作用胃癌细胞下YAP下游基因表达的影响

Fig.7 Effect of YAP overexpression on YAP downstream genes in quercetin-treated gastric cancer cells. A, B: Western blotting for analyzing the inhibitory effects of quercetin on YAP in YAP-overexpressing HGC-27 cells. C: mRNA expression of YAP and its downstream target genes CYR61 and CTGF in HGC-27 cells in Control, Control+Que (50 μmol/L), oe-YAP and oe-YAP+Que (50 μmol/L) groups. **P<0.01, ***P<0.001 vs Control group.

图8 过表达YAP对槲皮素作用胃癌细胞增殖、迁移和凋亡的影响

Fig.8 Effect of YAP overexpression on proliferation, migration, and apoptosis of quercetin-treated gastric cancer cells. A, B: EdU assays for assessing proliferation of quercetin-treated HGC-27 cells overexpressing YAP. C, D: Colony formation assays for assessing proliferation of quercetin-treated HGC-27 cells overexpressing YAP. E, F: Transwell migration assays of quercetin-treated HGC-27 cells overexpressing YAP (Scale bar=100 μm). G, H: Flow cytometry for assessing apoptosis of quercetin-treated HGC-27 cells overexpressing YAP. *P<0.05, **P<0.01, ***P<0.001 vs Control group.

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槲皮素通过调控Hippo通路蛋白YAP表达抑制胃癌细胞增殖与迁移并促进其凋亡

Quercetin inhibits proliferation and migration and promotes apoptosis of gastric cancer cells by promoting phosphorylation-mediated YAP inactivation

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