Mechanism of Liushenwan and Realgar in Inducing Apoptosis and DNA Damage in Human Endometrial Cancer JEC Cells

Zheng-yun LIU; Ying GOU; Nian JIANG; Huan WANG; Jie LIU

doi:10.13422/j.cnki.syfjx.20201421

您当前的位置：

首页 >

文章列表页 >

Mechanism of Liushenwan and Realgar in Inducing Apoptosis and DNA Damage in Human Endometrial Cancer JEC Cells

Pharmacology | 更新时间：2020-09-09

- Mechanism of Liushenwan and Realgar in Inducing Apoptosis and DNA Damage in Human Endometrial Cancer JEC Cells
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 14, Pages: 99-104(2020)
- 作者机构：
  
  遵义医科大学，贵州遵义 563000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201421
  CLC： R22;R242;R2-031;R285.5
- Published Online：06 May 2020，
  
  Published：20 July 2020
- 稿件说明：
移动端阅览
刘正芸,勾英,姜念等.六神丸和雄黄诱导子宫内膜癌细胞凋亡和DNA损伤的机制[J].中国实验方剂学杂志,2020,26(14):99-104.

LIU Zheng-yun,GOU Ying,JIANG Nian,et al.Mechanism of Liushenwan and Realgar in Inducing Apoptosis and DNA Damage in Human Endometrial Cancer JEC Cells[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(14):99-104.
刘正芸,勾英,姜念等.六神丸和雄黄诱导子宫内膜癌细胞凋亡和DNA损伤的机制[J].中国实验方剂学杂志,2020,26(14):99-104. DOI： 10.13422/j.cnki.syfjx.20201421.

LIU Zheng-yun,GOU Ying,JIANG Nian,et al.Mechanism of Liushenwan and Realgar in Inducing Apoptosis and DNA Damage in Human Endometrial Cancer JEC Cells[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(14):99-104. DOI： 10.13422/j.cnki.syfjx.20201421.

摘要

目的

比较经典名药六神丸和雄黄（As

）对子宫内膜癌细胞JEC的抗肿瘤作用及其机制。

方法

原子吸收法测定六神丸与As

中砷（As）的溶解度；噻唑蓝（MTT）比色法比较六神丸与As

对细胞增殖的抑制作用，细胞迁移实验比较六神丸与As

对细胞迁移的抑制作用；磷脂酰丝氨酸蛋白抗体/碘化丙啶（Annexin V-FITC/PI）双染结合流式细胞术比较六神丸与As

对细胞凋亡的影响，蛋白免疫印迹法（Western blot）比较六神丸与As

对凋亡和DNA损伤相关蛋白的影响。

结果

原子吸收法测定结果显示六神丸的As溶出量为17.4%，As

的As溶出量仅为1.6%。但在相同As含量的情况下，与As

组比较，六神丸3，10 mg·L

-1

组的细胞存活率明显降低（

0.05），六神丸0.25，0.5，1 mg·L

-1

组早期凋亡率明显增高（

0.05），六神丸1 mg·L

-1

组细胞迁移率明显下降（

0.05），六神丸1 mg·L

-1

组剪切的半胱氨酸天冬氨酸蛋白酶-3（cleaved Caspase-3），剪切的半胱氨酸天冬氨酸蛋白酶-7（cleaved Caspase-7），剪切的聚ADP核糖聚合酶（cleaved PARP）以及磷酸化的组蛋白（p-H

AX），磷酸化的检测点激酶2（p-CHK2），人共济失调毛细血管扩张症突变激酶（ATM）蛋白表达水平升高（

0.05），人共济失调毛细血管扩张症Rad3相关激酶（ATR）蛋白表达水平降低（

0.05），而Caspase-3和Caspase-7蛋白表达水平无明显改变。

结论

在等As剂量下，六神丸与As

均能抑制JEC细胞的增殖和迁移，诱导细胞凋亡和DNA损伤，但六神丸的效果优于As

，提示中药复方六神丸中还有其他成分协同As共同参与抗肿瘤作用。

Abstract

Objective

Compare the anti-tumor effect and mechanism of Liushenwan and realgar (As

) on human endometrial cancer cells JEC.

Method

The release of As

in Liushenwan and As

was measured by atomic absorption spectrometry. The 3-(4

5-dimethylthiazol-2-yl)-2

5-diphenyltetrazolium bromide (MTT) assay was used for cell proliferation

and cell migration was measured by Transwell assay. Flow cytometry and Western Blot were used to determine apoptosis and DNA damage.

Result

The dissolution of As in Liushenwan was 17.4%

and that of As

was only 1.6% according to atomic absorption assay. With the same content of As

compared with the As

group

the cell viability in the 3，10 mg·L

-1

Liushenwan groups was decreased (

0.05)

the early apoptosis rate was significantly increased in 0.25，0.5，1 mg·L

-1

Liushenwan groups (

0.05)

the rate of cell migration was decreased in 1 mg·L

-1

Liushenwan group (

0.05)

the expressions of cleaved cysteinyl aspartate-specific proteinase-3 (cleaved Caspase-3)

cleaved cysteinyl aspartate-specific proteinase-7 (cleaved Caspase-7)

cleaved poly ADP-ribose polymerase (cleaved PARP)

phosphorylated histone (p-H

AX)

phosphorylation of checkpoint kinase 2 (p-CHK2) and ataxia-telangiectasia mutated (ATM) were increased in 1 mg·L

-1

Liushenwan group (

0.05)

while the expression of phosphorylation of ataxia-telangiectasia mutated rad3-related (ATR) was decreased in 1 mg·L

-1

Liushenwan group (

0.05)

with no significant changes in the expressions of cysteinyl aspartate-specific proteinase-3 (Caspase-3) and cysteinyl aspartate-specific proteinase-7 (Caspase-7).

Conclusion

With the same content of As

both Liushenwan and As

could inhibit JEC cell proliferation and migration

and induce cell apoptosis and DNA damage. Liushenwan has a stronger effect than As

. It is suggested that there are other components in Liushenwan with an anti-tumor effect in cooperation with As.

关键词

Keywords

references

MITTAL P , KLINGLER-HOFFMANN M , ARENTZ G , et al . Proteomics of endometrial cancer diagnosis, treatment, and prognosis [J]. Proteomics Clin Appl , 2016 , 10 ( 3 ): 217 - 229 .

刘妮 , 闫雅欣 , 钱延玲 , 等 . 子宫内膜癌的治疗进展 [J]. 医药前沿 , 2016 , 6 ( 11 ): 5 - 7 .

侯倩倩 . 六神丸通过Wnt信号转导通路抗肿瘤的临床与实验研究 [D]. 济南：山东中医药大学 , 2011 .

刘寨东 , 齐元富 , 李秀荣 . 六神丸抗肿瘤实验研究进展 [J]. 山东中医杂志 , 2011 , 30 ( 7 ): 519 - 520 .

蔡国琴 , 张聪，郑礼 . 六神丸对肝癌BEL7402、肺癌A549和白血病HL60的体外抗肿瘤作用 [J]. 中成药 , 2012 , 34 ( 5 ): 935 - 936 .

李炜 , 赵玲 , 孙莉 , 等 . 六神丸抗肿瘤血管生成的体外实验研究 [J]. 山东中医杂志 , 2006 , 25 ( 6 ): 403 - 406 .

梁世霞 , 刘正芸 , 余丽梅 , 等 . 六神丸和砷化合物对人肝癌Hep3B细胞增殖的影响 [J]. 遵义医学院学报 , 2016 , 39 ( 6 ): 558 - 562 .

WANG J , LIN M , ZHANG T , et al . Arsenic(Ⅱ) sulfide quantum dots prepared by a wet process from its bulk [J]. J Am Chem Soc , 2008 , 130 ( 35 ): 11596 - 11597 .

QIN Y , WANG H , LIU Z , et al . Realgar quantum dots induce apoptosis and necrosis in HepG2 cells through endoplasmic reticulum stress [J]. Biomed Rep , 2015 , 3 ( 5 ): 657 - 662 .

WANG H , LIU Z , GOU Y , et al . Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway [J]. Int J Nanomedicine , 2015 , 2015 : 5505 - 5512 .

LIU J , WEI L X , WANG Q , et al . A review of cinnabar and/or realgar-containing traditional medicines [J]. J Ethnopharmacol , 2018 , doi: 10.1016/j.jep.2017.08.037 http://dx.doi.org/10.1016/j.jep.2017.08.037 .

岐黄 . 中药王国里的君臣佐使 [J]. 现代养生 , 2015 ( 12 ): 26 .

张保国，刘庆芳 . 六神丸的内科应用 [J]. 中成药 , 2006 , 28 ( 9 ): 1360 - 1362 .

杜建 . 中药抗肿瘤机制研究进展 [J]. 福建中医学院学报 , 2009 , 19 ( 4 ): 1 - 5 .

覃钰 , 金凤 , 金海 , 等 . 雄黄量子点和六神丸对荷瘤小鼠子宫颈癌的抑制作用 [J]. 中国新药与临床杂志 , 2015 , 34 ( 1 ): 64 - 67 .

WITTCHEN E S . Endothelial signaling in paracellular and transcellular leukocyte transmigration [J]. Front Biosci , 2009 , 14 ( 7 ): 2522 - 2545 .

史哲新 , 杨文华 , 汤毅 , 等 . 六神丸逆转白血病细胞多药耐药作用及相关机制研究 [J]. 天津中医药大学学报 , 2007 , 26 ( 1 ): 11 - 13 .

李炜 , 孟艳冬 , 赵玲 , 等 . 六神丸逆转灯盏细辛抑制MCF-7细胞凋亡作用的实验研究 [J]. 河北中医 , 2006 , 28 ( 12 ): 940 - 942 .

YANG J , XU Z P , HUANG Y , et al . ATM and ATR:Sensing DNA damage [J]. World J Gastroenterol , 2004 , 10 ( 2 ): 155 - 160 .

WANG J Y , CHEN S Y , SUN C N , et al . A central role of TRAX in the ATM-mediated DNA repair [J]. Oncogene , 2015 , 35 ( 13 ): 1657 - 1670 .

ROOS W P , KAINA B . DNA damage-induced cell death by apoptosis [J]. Trends Mol Med , 2006 , 12 ( 9 ): 440 - 450 .

WARMERDAM D O , KANAAR R . Dealing with DNA damage: relationships between checkpoint and repair pathways [J]. Mutat Res , 2010 , 704 ( 1/3 ): 2 - 11 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Protective Mechanism of Epigallocatechin Gallate (EGCG) and Procyanidins-B (PC-B ) on Liver Cell from AFB -induced DNA Damage

Shaoyaotang Containing Serum Mediates Fas/FasL Pathway to Inhibit Lipopolysaccharide Induced Inflammation and Apoptosis of Caco-2 Cells

Hei Xiaoyaosan Modulates Oxidative Stress and Apoptosis to Exert Neuroprotective Effect in Alzheimer's Disease Rats

Jujuboside A Improves Cognitive Function in Rat Model of VCI via PI3K/Akt Signaling Pathway

Effect of Serum Containing Zhenwutang on Apoptosis of Myocardial Mast Cells and Mitochondrial Autophagy

Related Author

JIA Liang

XIAO De-qiang

MA Ling-ling

FAN Qiu-yu

LIU Dan-dan

DENG Xiang-fa

HUANG Dong-ping

ZHANG Yong-sheng

Related Institution

The First Hospital of Hunan University of Chinese Medicine

People's Hospital of Ningxiang City，Ningxiang

Gansu University of Chinese Medicine

Gansu Key Laboratory of Traditional Chinese Medicine（TCM）Excavation and Innovative Transformation

Gansu Engineering Laboratory for New Products of TCM

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰