中国临床药理学杂志

丹皮酚通过调控miR-128-3p/NEK2信号轴对卵巢癌细胞上皮间质转化及内质网应激诱导的细胞凋亡影响的研究

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赵贝贝 ^1a , 滑天 ^1b , 王瑞敏 ^1a , 王晓慧 ^1a

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(21): 3083-3089

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (21) : 3083 -3089

丹皮酚通过调控miR-128-3p/NEK2信号轴对卵巢癌细胞上皮间质转化及内质网应激诱导的细胞凋亡影响的研究

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赵贝贝^1a, 滑天^1b, 王瑞敏^1a, 王晓慧^1a

作者信息

^1a.邢台市人民医院妇四科，河北邢台 054000

^1b.邢台市人民医院妇五科，河北邢台 054000

通讯作者:

滑天，主任医师，博士生导师 MP: 13931941630 E-mail: zbb4423@163.com

作者简介:

赵贝贝（1990-），女，主治医师，主要从事妇科肿瘤方面的临床工作和研究

Research of paeonol influences the epithelial-mesenchymal transition in ovarian cancer cells and endoplasmic reticulum stress-induced apoptosis by regulating the miR-128-3p/NEK2 signaling axis

Bei-bei ZHAO^1a, Tian HUA^1b, Rui-min WANG^1a, Xiao-hui WANG^1a

Affiliations

^1a.Fourth Gynaecology Department, Xingtai People’s Hospital, Xingtai 054000, Hebei Province, China

^1b.Fifth Gynaecology Department, Xingtai People’s Hospital, Xingtai 054000, Hebei Province, China

出版时间: 2025-11-17 doi: 10.13699/j.cnki.1001-6821.2025.21.014

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摘要

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目的

探究丹皮酚（PAE）通过调控微小RNA-128-3p（miR-128-3p）/永离有丝分裂基因A相关激酶2（NEK2）信号轴对卵巢癌细胞上皮间质转化（EMT）及内质网应激诱导的细胞凋亡的影响。

方法

将SKOV3细胞分为SKOV3组（正常培养）、PAE组（4 mmol·L^-1 PAE处理）、inhibitor-NC组（转染miR-128-3p inhibitor阴性对照）、miR-128-3p inhibitor组（转染miR-128-3p inhibitor）、si-NC组（转染si-NEK2阴性对照）、si-NEK2组（转染si-NEK2）、PAE+inhibitor-NC组（基于PAE组，转染miR-128-3p inhibitor阴性对照）、PAE+miR-128-3p inhibitor组（基于PAE组，转染miR-128-3p inhibitor）、PAE+miR-128-3p inhibitor+si-NC组（基于PAE组，共转染miR-128-3p inhibitor和si-NEK2阴性对照）和PAE+miR-128-3p inhibitor+si-NEK2组（基于PAE组，共转染miR-128-3p inhibitor和si-NEK2）。用实时荧光定量聚合酶链反应（PCR）检测mRNA相对表达水平；用免疫荧光法检测NEK2蛋白的阳性表达；用蛋白质印迹法检测相关蛋白的相对表达水平。

结果

SKOV3组、PAE组、PAE+inhibitor-NC组和PAE+miR-128-3p inhibitor组的miR-128-3p相对表达水平分别为1.00±0.12、2.34±0.27、2.30±0.29和1.19±0.21，NEK2 mRNA相对表达水平分别为1.00±0.13、0.58±0.09、0.61±0.12和0.93±0.18，NEK2的阳性表达分别为1.00±0.11、0.29±0.05、0.31±0.06和0.94±0.17；SKOV3组、PAE组、PAE+inhibitor-NC组、PAE+miR-128-3p inhibitor组、PAE+miR-128-3p inhibitor+si-NC组和PAE+miR-128-3p inhibitor+si-NEK2组的E-钙黏蛋白（E-cadherin）mRNA相对表达水平分别为1.00±0.12、2.25±0.29、2.27±0.34、1.30±0.21、1.32±0.20和2.03±0.35，N-钙黏蛋白（N-cadherin）mRNA相对表达水平分别为1.00±0.14、0.60±0.09、0.63±0.12、0.92±0.17、0.94±0.18和0.67±0.13，波形蛋白（Vimentin）mRNA相对表达水平分别为1.00±0.13、0.62±0.09、0.66±0.11、0.90±0.17、0.92±0.18和0.71±0.13，激活转录因子4（ATF4）蛋白相对表达水平分别为1.00±0.11、3.22±0.57、3.31±0.60、1.51±0.24、1.49±0.21和2.97±0.44，CAAT区/增强子结合蛋白（C/EBP）同源蛋白（CHOP）相对表达水平分别为1.00±0.14、3.85±0.47、3.62±0.41、1.31±0.17、1.28±0.17和3.26±0.57，切割型半胱天冬酶-3（Cleaved-caspase-3）蛋白相对表达水平分别为1.00±0.13、4.52±0.67、4.61±0.71、1.67±0.26、1.69±0.31和4.11±0.76，PAE组的上述指标与SKOV3组比较；PAE+miR-128-3p inhibitor组的上述指标与PAE+inhibitor-NC组比较；PAE+miR-128-3p inhibitor+si-NEK2组的上述指标与PAE+miR-128-3p inhibitor+si-NC组比较，在统计学上差异均有统计学意义（均P<0.05）。

结论

PAE对卵巢癌具有抑制EMT，促进内质网应激诱导的细胞凋亡的作用，该作用可能是通过上调miR-128-3p抑制NEK2表达实现的。

关键词

丹皮酚 / 微小核糖核酸-128-3p / 永离有丝分裂基因A相关激酶2 / 卵巢癌 / 上皮间质转化 / 内质网应激

Abstract

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Objective

To investigate the effect of paeonol (PAE) on epithelial-mesenchymal transition (EMT) and endoplasmic reticulum stress-induced apoptosis in ovarian cancer cells by regulating the microRNA-128-3p (miR-128-3p)/ never in mitosis gene A-related kinase 2 (NEK2) signaling axis.

Methods

SKOV3 cells were divided into the following groups: SKOV3 group (normal culture), PAE group (4 mmol·L^-1 PAE treatment), inhibitor-NC group (transfected with miR-128-3p inhibitor negative control), miR-128-3p inhibitor group (transfected with miR-128-3p inhibitor), si-NC group (transfected with si-NEK2 negative control), si-NEK2 group (transfected with si-NEK2), PAE+inhibitor-NC group (based on the PAE group, transfected with miR-128-3p inhibitor negative control), PAE+miR-128-3p inhibitor group (based on the PAE group, transfected with miR-128-3p inhibitor), PAE+miR-128-3p inhibitor+si-NC group (based on the PAE group, co-transfected with miR-128-3p inhibitor and si-NEK2 negative control) and PAE+miR-128-3p inhibitor+si-NEK2 group (based on the PAE group, co-transfected with miR-128-3p inhibitor and si-NEK2). Quantitative real-time polymerase chain reaction (PCR) was used to detect the relative expression levels of mRNA; immunofluorescence was used to detect the positive expression of NEK2 protein; Western blot was used to detect the relative expression levels of related proteins.

Results

The relative expression levels of miR-128-3p in SKOV3 group, PAE group, PAE+inhibitor-NC group and PAE+miR-128-3p inhibitor group were 1.00±0.12, 2.34±0.27, 2.30±0.29 and 1.19±0.21, respectively; the relative expression levels of NEK2 mRNA were 1.00±0.13, 0.58±0.09, 0.61±0.12 and 0.93±0.18, respectively; the positive expression of NEK2 was 1.00±0.11, 0.29±0.05, 0.31±0.06 and 0.94±0.17, respectively; the relative expression levels of E-cadherin mRNA in SKOV3 group, PAE group, PAE+inhibitor-NC group, PAE+miR-128-3p inhibitor group, PAE+miR-128-3p inhibitor+si-NC group and PAE+miR-128-3p inhibitor+si-NEK2 group were 1.00±0.12, 2.25±0.29, 2.27±0.34, 1.30±0.21, 1.32±0.20 and 2.03±0.35, respectively; the relative expression levels of N-cadherin mRNA were 1.00±0.14, 0.60±0.09, 0.63±0.12, 0.92±0.17, 0.94±0.18 and 0.67±0.13, respectively; the relative expression levels of Vimentin mRNA were 1.00±0.13, 0.62±0.09, 0.66±0.11, 0.90±0.17, 0.92±0.18 and 0.71±0.13, respectively; the relative expression levels of activating transcription factor 4 (ATF4) protein were 1.00±0.11, 3.22±0.57, 3.31±0.60, 1.51±0.24, 1.49±0.21 and 2.97±0.44, respectively; the relative expression levels of CCAAT/ enhancer binding protein (C/EBP) homologous protein (CHOP) were 1.00±0.14, 3.85±0.47, 3.62±0.41, 1.31±0.17, 1.28±0.17 and 3.26±0.57, respectively; the relative expression levels of cleaved-caspase-3 were 1.00±0.13, 4.52±0.67, 4.61±0.71, 1.67±0.26, 1.69±0.31 and 4.11±0.76, respectively. The differences in the above indicators were statistically significant when comparing PAE group with SKOV3 group, PAE+miR-128-3p inhibitor group with PAE+inhibitor-NC group and PAE+miR-128-3p inhibitor+si-NEK2 group with PAE+miR-128-3p inhibitor+si-NC group (all P<0.05).

Conclusion

PAE suppresses EMT and promotes endoplasmic reticulum stress-induced apoptosis in ovarian cancer cells, potentially by upregulating miR-128-3p to inhibit NEK2 expression.

Key words

paeonol / micro ribonucleicacid-128-3p / never in mitosis gene A -related kinase 2 / ovarian cancer / epithelial-mesenchymal transition / endoplasmic reticulum stress

引用本文

赵贝贝, 滑天, 王瑞敏, 王晓慧. 丹皮酚通过调控miR-128-3p/NEK2信号轴对卵巢癌细胞上皮间质转化及内质网应激诱导的细胞凋亡影响的研究. 中国临床药理学杂志, 2025 , 41 (21) : 3083 -3089 . DOI: 10.13699/j.cnki.1001-6821.2025.21.014

Bei-bei ZHAO, Tian HUA, Rui-min WANG, Xiao-hui WANG. Research of paeonol influences the epithelial-mesenchymal transition in ovarian cancer cells and endoplasmic reticulum stress-induced apoptosis by regulating the miR-128-3p/NEK2 signaling axis[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (21) : 3083 -3089 . DOI: 10.13699/j.cnki.1001-6821.2025.21.014

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2025年第41卷第21期

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doi: 10.13699/j.cnki.1001-6821.2025.21.014

接收时间：2025-05-11
首发时间：2026-08-05
出版时间：2025-11-17

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收稿日期：2025-05-11

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^1a.邢台市人民医院妇四科，河北邢台 054000

^1b.邢台市人民医院妇五科，河北邢台 054000

通讯作者:

滑天，主任医师，博士生导师 MP: 13931941630 E-mail: zbb4423@163.com

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
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