中国临床药理学杂志

柚皮素抑制JAK2/STAT3通路对食管癌细胞增殖和凋亡的研究

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牛朝霞 ^1a , 杨丽娜 ^1b , 张瑾钰 ^1a , 陈洁 ^1a

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(9): 1277-1283

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (9) : 1277 -1283

柚皮素抑制JAK2/STAT3通路对食管癌细胞增殖和凋亡的研究

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牛朝霞^1a, 杨丽娜^1b, 张瑾钰^1a, 陈洁^1a

作者信息

^1a.河南医学高等专科学校，基础医学部，河南郑州 451191

^1b.河南医学高等专科学校，医学技术系，河南郑州 451191

通讯作者:

陈洁，教授，博士生导师 MP: 13633801260 E-mail: qhoq87@163.com

作者简介:

牛朝霞（1979-），女，副教授，主要从事病理生理学方面的教学与科研工作

Research of naringenin on the proliferation and apoptosis of esophageal cancer cells by suppressing the JAK2/STAT3 pathway

Zhao-xia NIU^1a, Li-na YANG^1b, Jin-yu ZHANG^1a, Jie CHEN^1a

Affiliations

^1a.Department of Basic Medicine, Henan Medical College, Zhengzhou 451191, Henan Province, China

^1b.Department of Medical Technology, Henan Medical College, Zhengzhou 451191, Henan Province, China

出版时间: 2026-05-17 doi: 10.13699/j.cnki.1001-6821.2026.09.013

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摘要

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目的

探究柚皮素抑制非受体型酪氨酸激酶2/信号转导与转录激活因子3（JAK2/STAT3）通路对食管癌细胞增殖和凋亡作用及其机制。

方法

用细胞计数试剂盒-8（CCK-8）筛选不同剂量柚皮素对KYSE150细胞活力的影响以选择柚皮素浓度。将KYSE150细胞依次分为对照组（常规培养）、低剂量实验组（10 μmol·L^-1柚皮素）、高剂量实验组（40 μmol·L^-1柚皮素）、JAK2/STAT3通路抑制剂组（20 μmol·L^-1 AG490）、JAK2/STAT3通路激活剂组（40 μmol·L^-1柚皮素和10 μmol·L^-1香豆霉素A1）。用5-溴-2’-脱氧尿苷（Brdu）染色法检测细胞Brdu阳性细胞率，用克隆形成实验法检测细胞克隆形成数量，用逆转录实时荧光定量聚合酶链反应（RT-qPCR）法检测增殖和凋亡相关基因表达，用流式细胞仪法检测细胞凋亡率，用末端脱氧核苷酸转移酶介导的2’-脱氧尿苷-5’-三磷酸缺口末端标记（TUNEL）染色法检测细胞TUNEL阳性率，用蛋白质印迹法检测JAK2/STAT3通路相关蛋白表达，用免疫组化法检测柚皮素对KYSE150细胞裸鼠异种移植瘤Ki-67核抗原（Ki67）和肿瘤组织生长的影响。

结果

柚皮素对KYSE150细胞活力半数抑制浓度接近40 μmol·L^-1。对照组、低剂量实验组、高剂量实验组、JAK2/STAT3通路抑制剂组和JAK2/STAT3通路激活剂组KYSE150细胞Brdu阳性率分别为（58.64±5.23）%、（46.23±4.05）%、（21.05±3.04）%、（23.62±3.15）%和（35.98±3.21）%；克隆形成数分别为（102.36±10.25）、（78.64±7.21）、（50.05±4.32）、（52.39±5.03）和（61.55±5.12）个；细胞周期蛋白B1（CyclinB1）信使核糖核酸（mRNA）相对表达水平分别为1.02±0.11、0.74±0.05、0.45±0.04、0.48±0.05和0.62±0.06；细胞周期蛋白依赖性激酶1（CDK1）mRNA相对表达水平分别为1.03±0.07、0.62±0.05、0.27±0.03、0.30±0.04和0.51±0.04；凋亡率分别为（4.15±0.42）%、（15.62±1.02）%、（29.65±2.03）%、（27.84±1.98）%和（19.66±1.20）%；TUNEL阳性率分别为（8.65±0.82）%、（20.64±2.03）%、（37.68±3.05）%、（35.62±2.16）%和（28.14±2.01）%；B细胞淋巴瘤-特大号蛋白（Bcl-xl）mRNA相对表达水平分别为1.02±0.07、0.72±0.06、0.41±0.04、0.44±0.05和0.59±0.05；B细胞淋巴瘤-2蛋白（Bcl-2）mRNA相对表达水平分别为1.01±0.05、0.59±0.04、0.36±0.03、0.39±0.04和0.50±0.03。低剂量实验组、高剂量实验组以及JAK2/STAT3通路抑制剂组与对照组相比，高剂量实验组以及JAK2/STAT3通路抑制剂组与低剂量实验组相比，JAK2/STAT3通路激活剂组与高剂量实验组相比，上述指标在统计学上差异均有统计学意义（均P<0.05）。在裸鼠实验中，动物对照组、动物低剂量实验组和动物高剂量实验组肿瘤体积分别为（1 287.65±98.54）、（821.22±71.65）和（425.39±37.69）mm³；肿瘤质量分别为（1.85±0.12）、（1.20±0.09）和（0.73±0.05）g；肿瘤组织中Ki67阳性率分别为（69.52±5.36）%、（44.35±3.12）%和（20.06±2.85）%。动物低、高剂量实验组的上述指标与动物对照组相比，动物高剂量实验组的上述指标与动物低剂量实验组相比，在统计学上差异均有统计学意义（均P<0.05）。

结论

柚皮素通过抑制JAK2/STAT3信号通路，显著抑制食管癌KYSE150细胞的增殖并促进其凋亡。

关键词

柚皮素 / 食管癌 / 非受体型酪氨酸激酶2/信号转导与转录激活因子3通路 / 细胞增殖 / 凋亡

Abstract

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Objective

To investigate the effects and mechanism of naringenin inhibiting the non-receptor tyrosine kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway on the proliferation and apoptosis of esophageal cancer cells.

Methods

The effects of different doses of naringenin on KYSE150 cell viability was screened using cell counting kit-8 (CCK-8), and naringenin concentration was selected. KYSE150 cells were sequentially divided into control group (conventional culture), low-dose experimental group (10 μmol·L^-1 naringenin), high-dose experimental group (40 μmol·L^-1 naringenin), JAK2/STAT3 pathway inhibitor group (20 μmol·L^-1 AG490) and JAK2/STAT3 pathway activator group (40 μmol·L^-1 naringenin and 10 μmol·L^-1 coumermycin A1). The 5-bromo-2 ’- deoxyuridine (Brdu) positive cell rate was detected using the Brdu staining method, the number of cell clones formed was detected using the clone formation assay, the expression of proliferation and apoptosis related genes was detected using reverse transcription real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), the apoptosis rate was detected using flow cytometry, the terminal deoxynucleotide transferase mediated 2’-deoxyuridine-5’- triphosphate notch end labeling (TUNEL) positive rate was detected using the TUNEL staining method, the expression of JAK2/STAT3 pathway related proteins was detected using Western blot, and the effect of naringenin on the growth of KYSE150 xenograft tumors Ki-67 nuclear antigen (Ki67) and tumor tissues growth in nude mice was detected using immunohistochemistry.

Results

The half maximal inhibitory concentration of naringenin on KYSE150 cell viability is close to 40 μmol·L^-1. The Brdu positivity rates of KYSE150 cells in control group, low-dose experimental group, high-dose experimental group, JAK2/STAT3 pathway inhibitor group and JAK2/STAT3 pathway activator group were (58.64±5.23)%, (46.23±4.05)%, (21.05±3.04)%, (23.62±3.15)% and (35.98±3.21)%, respectively; the clone formation numbers were (102.36±10.25), (78.64±7.21), (50.05±4.32), (52.39±5.03) and (61.55±5.12) cells, respectively; the relative expression levels of CyclinB1 messenger ribonucleic aeid (mRNA) were 1.02±0.11, 0.74±0.05, 0.45±0.04, 0.48±0.05 and 0.62±0.06, respectively; the relative expression levels of cyclin dependent kinase 1 (CDK1) mRNA were 1.03±0.07, 0.62±0.05, 0.27±0.03, 0.30±0.04 and 0.51±0.04, respectively; the apoptosis rates were (4.15±0.42)%, (15.62±1.02)%, (29.65±2.03)%, (27.84±1.98)% and (19.66±1.20)%, respectively; the positive rates of TUNEL were (8.65±0.82)%, (20.64±2.03)%, (37.68±3.05)%, (35.62±2.16)% and (28.14±2.01)%, respectively; the relative expression levels of Bcl-xl mRNA were 1.02±0.07, 0.72±0.06, 0.41±0.04, 0.44±0.05 and 0.59±0.05, respectively; the relative expression levels of Bcl-2 mRNA were 1.01±0.05, 0.59±0.04, 0.36±0.03, 0.39±0.04 and 0.50±0.03, respectively. Compared control group with low-dose experimental group, high-dose experimental group and JAK2/STAT3 pathway inhibitor group, compared low-dose experimental group with high-dose experimental group and JAK2/STAT3 pathway inhibitor group, compared high-dose experimental group with JAK2/STAT3 pathway activator group, the above indicators all showed statistically significant differences (all P<0.05). In nude mouse experiments, the tumor volumes of animal control group, animal low-dose experimental group and animal high-dose experimental group were (1 287.65±98.54), (821.22±71.65) and (425.39±37.69) mm³, respectively; the tumor masses were (1.85±0.12), (1.20±0.09) and (0.73±0.05) g, respectively; the Ki67 positivity rates in tumor tissues were (69.52±5.36)%, (44.35±3.12)% and (20.06±2.85)%, respectively. The above indicators of the animal low and high-dose experimental groups were statistically significantly different from those of animal control group, and the above indicators of the animal high-dose experimental group were statistically significantly different from those of animal low-dose experimental group (all P<0.05).

Conclusion

Naringenin clearly inhibits the proliferation and promotes apoptosis of esophageal cancer KYSE150 cells by suppressing the JAK2/STAT3 signaling pathway.

Key words

naringenin / Janus kinase 2/signal transducer and activator of transcription 3 pathway / esophageal cancer / cell proliferation / apoptosis

引用本文

牛朝霞, 杨丽娜, 张瑾钰, 陈洁. 柚皮素抑制JAK2/STAT3通路对食管癌细胞增殖和凋亡的研究. 中国临床药理学杂志, 2026 , 42 (9) : 1277 -1283 . DOI: 10.13699/j.cnki.1001-6821.2026.09.013

Zhao-xia NIU, Li-na YANG, Jin-yu ZHANG, Jie CHEN. Research of naringenin on the proliferation and apoptosis of esophageal cancer cells by suppressing the JAK2/STAT3 pathway[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (9) : 1277 -1283 . DOI: 10.13699/j.cnki.1001-6821.2026.09.013

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河南省科技厅科技攻关基金资助项目(262102310137)

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2026年第42卷第9期

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doi: 10.13699/j.cnki.1001-6821.2026.09.013

接收时间：2026-01-07
首发时间：2026-08-06
出版时间：2026-05-17

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收稿日期：2026-01-07

基金

河南省科技厅科技攻关基金资助项目(262102310137)

作者信息

^1a.河南医学高等专科学校，基础医学部，河南郑州 451191

^1b.河南医学高等专科学校，医学技术系，河南郑州 451191

通讯作者:

陈洁，教授，博士生导师 MP: 13633801260 E-mail: qhoq87@163.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2026.09.013

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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
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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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