GSK-J4通过抑制STAT3磷酸化对HepG2肝癌细胞凋亡和侵袭的影响

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GSK-J4通过抑制STAT3磷酸化对HepG2肝癌细胞凋亡和侵袭的影响

基础医学 | 更新时间：2026-01-09

- GSK-J4通过抑制STAT3磷酸化对HepG2肝癌细胞凋亡和侵袭的影响
- Jmjd3 inhibitor GSK-J4 induces apoptosis and attenuates invasion in HepG2 cells by inhibiting STAT3 phosphorylation
- 第三军医大学学报 2018年40卷第9期页码：739-745
- 作者机构：
  
  400016 重庆, 重庆医科大学附属第一医院肝胆外科
- 作者简介：
  
  [吴忠均, E-mail:wzjtcy@126.com WU Zhongjun, E-mail:wzjtcy@126.com
- 基金信息：
  
  国家自然科学基金面上项目(81672959)
- DOI：10.16016/j.1000-5404.201710224
  中图分类号： R73-361;R735.7;R979.19
- 收稿：2017-10-31，
  
  修回：2018-02-22，
  
  纸质出版：2018-05-15
- 稿件说明：
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陈青松, 万磊, 周壮, 等. GSK-J4通过抑制STAT3磷酸化对HepG2肝癌细胞凋亡和侵袭的影响[J]. 第三军医大学学报, 2018,40(9):739-745.

Qingsong CHEN, Lei WAN, Zhuang ZHOU, et al. Jmjd3 inhibitor GSK-J4 induces apoptosis and attenuates invasion in HepG2 cells by inhibiting STAT3 phosphorylation[J]. Journal of Third Military Medical University, 2018, 40(9): 739-745.
陈青松, 万磊, 周壮, 等. GSK-J4通过抑制STAT3磷酸化对HepG2肝癌细胞凋亡和侵袭的影响[J]. 第三军医大学学报, 2018,40(9):739-745. DOI： 10.16016/j.1000-5404.201710224.

Qingsong CHEN, Lei WAN, Zhuang ZHOU, et al. Jmjd3 inhibitor GSK-J4 induces apoptosis and attenuates invasion in HepG2 cells by inhibiting STAT3 phosphorylation[J]. Journal of Third Military Medical University, 2018, 40(9): 739-745. DOI： 10.16016/j.1000-5404.201710224.

摘要

目的

2

探讨GSK-J4通过抑制组蛋白去甲基化酶含Jumonji结构域蛋白3 (Jumonji domain-containing protein 3

Jmjd3)并上调H3K27me3的表达影响HepG2肝癌细胞凋亡和侵袭的分子机制。

方法

2

体外培养人正常肝细胞L02及人肝细胞肝癌(hepatocellular carcinoma

HCC)细胞株HepG2、SMMC7721

RT-PCR检测Jmjd3 mRNA表达

Western blot检测Jmjd3、H3K27me3蛋白表达; CCK-8法检测不同浓度GSK-J4 (0、10、30、50 μmol/mL)处理HepG2后增殖能力; 流式细胞仪检测凋亡率; Transwell检测细胞侵袭力; Western blot检测Jmjd3、H3K27me3和凋亡相关蛋白Bcl2、Bax、Caspase3、上皮细胞间质转化(epithelial-mesenchymal transition

EMT)相关标记物E-钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)以及p-STAT3、STAT3蛋白表达。

结果

2

与L02比

Jmjd3高表达

H3K27me3低表达于HepG2、SMMC7721肝癌细胞株(

P

<

0.05);GSK-J4抑制HepG2增殖(

P

<

0.05);GSK-J4处理组细胞凋亡率明显提高

细胞侵袭能力减弱(

P

<

0

.05);GSK-J4处理HepG2后Jmjd3水平降低

H3K27me3水平增高

Bcl2水平降低

Bax、Caspase3水平增高

E-cadherin表达增高

Vimentin水平降低(

P

<

0.05);p-STAT3表达下调(

P

<

0.01)。

结论

2

GSK-J4通过抑制Jmjd3并上调H3K27me3表达而诱导HepG2发生凋亡并减弱侵袭

其可能与抑制EMT形成和STAT3的磷酸化有关。

Abstract

Objective

2

To determine the effect of GSK-J4 on apoptosis and invasion in HepG2 cells by inhibiting histone demethylase Jumonji domain-containing protein 3 (Jmjd3) and modifying H3K27me3

and mine its underlying mechanism.

Methods

2

Human normal hepatocytes L02 and hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC7721 were employed in this study.The mRNA expression of Jmjd3 was detected by RT-PCR

and its protein level and that of H3K27me3 were measured by Western blotting.CCK-8 assay was used to detect the proliferation of HepG2 cells after the treatment of different concentrations of GSK-J4 (0

10

30 and 50 μmol/mL) treatment.Flow cytometry and Transwell chamber test were used respectively to detect cell apoptosis and invasion ability.The expression levels of Jmjd3 and H3K27me3

apoptosis related proteins Bcl2

Bax and Caspase3

epithelial-mesenchymal transition (EMT) markers E-cadherin and Vimentin

and p-STAT3 and STAT3 were detected by Western blotting.

Results

2

Jmjd3 was significantly highly expressed

while H3K27me3 was lowly expressed in HCC cell lines HepG2 and SMMC7721 when compared with the L02 cells (

P

<

0.05).GSK-J4 treatment inhibited the proliferation of HepG2 cells (

P

<

0.05)

increased cell apoptotic rate

weakened invasion ability (

P

<

0.05)

decreased the expression of Jmjd3 while elevated that of H3K27me3.The treatment also resulted in the decrease of Bcl2 level

increases of Bax and Caspase3 levels

elevation of E-cadherin

but reduce of Vimentin level (

P

<

0.05)

and inhibition of STAT3 phosphorylation (

P

<

0.01).

Conclusion

2

GSK-J4 induces apoptosis and suppresses the invasion ability in HepG2 cells by inhibiting Jmjd3 and up-regulating H3K27me3

which may be related to the suppression of EMT formation and STAT3 phosphorylation.

关键词

Keywords

references

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