香叶木素通过调节Hippo通路对胰腺癌细胞增殖迁移和侵袭及上皮间质转化的影响

doi:10.3969/j.issn.1006-6233.2025.03.03

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摘要 目的: 探究香叶木素(DIO)通过调节Hippo通路对胰腺癌细胞增殖、迁移和侵袭及上皮间质转化(EMT)的影响。方法: 0.625~20μg/mL的香叶木素处理人胰腺癌细胞(PANC-1),检测细胞活性,选出香叶木素最佳的实验浓度。将PANC-1细胞随机分为Control组、香叶木素低、中、高浓度组(D-L组、D-M组、D-H组)、YAP抑制剂维替泊芬组(VP组)。除Control组外,其余组细胞分别进行相应药物干预;检测香叶木素对PANC-1细胞增殖、迁移、侵袭的影响;Wesern Blot检测相关蛋白表达;小鼠移植瘤检测香叶木素对胰腺癌移植瘤生长的影响。结果: 筛选出2.5μg/mL、5.0μg/mL、10.0μg/mL香叶木素浓度用于后续实验。与Control组比较,D-L、D-M、D-H组PANC-1细胞Edu阳性率、划痕愈合率、细胞侵袭数量降低,PCNA、MMP-2、MMP-9、N-Cadherin、Vimentin表达下调,E-Cadherin、p-YAP/YAP、p-TAZ/TAZ表达上调(P<0.05);与D-H组比较,VP组Edu阳性率、划痕愈合率、细胞侵袭数量上调,PCNA、MMP-2、MMP-9、N-Cadherin、Vimentin表达上调,E-Cadherin、p-YAP/YAP、p-TAZ/TAZ表达下调(P<0.05)。香叶木素组裸鼠移植瘤体积和重量比对照组低,p-YAP/YAP、p-TAZ/TAZ表达上调(P<0.05)。结论: 香叶木素通过激活Hippo通路抑制胰腺癌细胞增殖、迁移和侵袭及EMT。

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关键词 ：香叶木素, 胰腺癌, Hippo通路, 增殖, 迁移, 侵袭, 上皮间质转化

Abstract：Objective: To investigate the effects of diosmetin (DIO) on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Hippo pathway. Methods: Human pancreatic cancer cells (PANC-1) were treated with diosmetin at concentrations ranging from 0.625μg/mL to 20 μg/mL to determine the optimal experimental concentration. PANC-1 cells were divided into the following groups: Control group, low-concentration diosmetin group (D-L), medium-concentration diosmetin group (D-M), high-concentration diosmetin group (D-H), and YAP inhibitor verteporfin group (VP). Except for the Control group, cells in the other groups were treated with the corresponding drugs. The effects of diosmetin on PANC-1 cell proliferation, migration, and invasion were assessed. Protein expression was detected by Western blotting, and the impact of diosmetin on pancreatic cancer xenograft growth was evaluated in a mouse model. Results: Diosmetin concentrations of 2.5μg/mL, 5.0μg/mL, and 10.0μg/mL were selected for subsequent experiments. Compared to the Control group, the D-L, D-M, and D-H groups showed reduced Edu-positive rates, scratch healing rates, and cell invasion numbers, along with downregulated expression of PCNA, MMP-2, MMP-9, N-cadherin, and vimentin, and upregulated expression of E-cadherin, p-YAP/YAP, and p-TAZ/TAZ (P<0.05). Compared to the D-H group, the VP group exhibited increased Edu-positive rates, scratch healing rates, and cell invasion numbers, upregulated expression of PCNA, MMP-2, MMP-9, N-cadherin, and vimentin, and downregulated expression of E-cadherin, p-YAP/YAP, and p-TAZ/TAZ (P<0.05). In the mouse xenograft model, the diosmetin group showed reduced tumor volume and weight, along with upregulated expression of p-YAP/YAP and p-TAZ/TAZ (P<0.05). Conclusion: Diosmetin inhibits the proliferation, migration, invasion, and EMT of pancreatic cancer cells by activating the Hippo pathway.

Key words： Diosmetin Pancreatic cancer Hippo pathway Proliferation Migration Invasion Epithelial-mesenchymal transition

基金资助:河北省2024年度医学科学研究课题计划,(编号:20240263)

通讯作者: 张振亮

引用本文:

赵兴龙, 郝净, 张振亮. 香叶木素通过调节Hippo通路对胰腺癌细胞增殖迁移和侵袭及上皮间质转化的影响[J]. 河北医学, 2025, 31(3): 368-373.
ZHAO Xinglong, et al. Effects of Diosmetin on Proliferation Migration Invasion and Epithelial-Mesenchymal Transition in Pancreatic Cancer Cells via Regulation of the Hippo Pathway. HeBei Med, 2025, 31(3): 368-373.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.03.03 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I3/368

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