anti-ER<sup>+</sup> breast cancer by activating endoplasmic reticulum stress to induce apoptosis

Lie YUAN; Weiying ZHOU; Duanfang ZHOU; Xu LIU; Xiaoli LI

doi:10.16016/j.2097-0927.202304042

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anti-ER⁺ breast cancer by activating endoplasmic reticulum stress to induce apoptosis

Basic Medicine | 更新时间：2026-01-09

- anti-ER⁺ breast cancer by activating endoplasmic reticulum stress to induce apoptosis
- Journal of Army Medical University Vol. 45, Issue 19, Pages: 2065-2073(2023)
- 作者机构：
  
  1.400016 重庆，重庆医科大学：药学院药理学系
  2.400016 重庆，重庆医科大学：药物代谢研究重庆市重点实验室
  3.610031 成都，成都市第三人民医院药学部
- 作者简介：
- 基金信息：
  
  the General Program of Natural Science Foundation of Chongqing(cstc2020jcyjmsxmX0223);the Postgraduate Research and Innovation Project of Chongqing(CYS22371)
- DOI：10.16016/j.2097-0927.202304042
  CLC： R285.5;R730.53;R737.9
- Received：11 April 2023，
  
  Revised：2023-06-01，
  
  Published：15 October 2023
- 稿件说明：
移动端阅览
Lie YUAN, Weiying ZHOU, Duanfang ZHOU, et al. anti-ER⁺ breast cancer by activating endoplasmic reticulum stress to induce apoptosis[J]. Journal of Army Medical University, 2023, 45(19): 2065-2073.
DOI：

Lie YUAN, Weiying ZHOU, Duanfang ZHOU, et al. anti-ER⁺ breast cancer by activating endoplasmic reticulum stress to induce apoptosis[J]. Journal of Army Medical University, 2023, 45(19): 2065-2073. DOI： 10.16016/j.2097-0927.202304042.

摘要

目的

探讨雷公藤红素(celastrol

Cel)通过激活内质网应激介导的细胞凋亡发挥抗雌激素受体阳性(estrogen receptor positive

)乳腺癌的作用机制。

方法

以ER

人乳腺癌细胞系MCF-7与T47D为研究对象，采用MTT与细胞克隆实验检测Cel对细胞活力与增殖的影响；采用Western blot检测Cel对凋亡相关蛋白表达的影响；分别采用RT-qPCR和Western blot检测Cel对内质网应激相关基因和蛋白表达的影响；体内建立MCF-7细胞裸鼠原位移植瘤模型，观察Cel对移植瘤生长的影响。

结果

MTT与细胞克隆实验结果显示，Cel可呈

剂量依赖性抑制MCF-7与T47D细胞活力与增殖(

＜0.05)；Western blot结果显示，Cel可上调凋亡相关蛋白Cleaved PARP与BAX表达，并下调BCL-2表达(

＜0.05)；RT-qPCR结果显示，Cel可上调内质网应激相关基因IRE1α、ATF6、PERK、ATF4、CHOP、BIP的表达水平(

＜0.05)；Cel可诱导内质网应激标志蛋白BIP表达升高，PERK通路相关蛋白p-PERK、p-eIF2α、ATF4、CHOP表达增加，IRE1α通路相关蛋白p-IRE1α、XBP1s表达增加，ATF6通路中的Cleaved ATF6水平增加；体内实验结果显示，Cel能显著降低裸鼠原位移植瘤的体积(

＜0.05)，且对裸鼠体质量无明显的影响。

结论

Cel具有一定的抑制ER

乳腺癌MCF-7及T47D细胞增殖的作用，其机制可能与激活内质网应激信号通路从而诱导细胞凋亡有关。

Abstract

Objective

To investigate the mechanism of celastrol (Cel) against estrogen receptor positive (ER

) breast cancer by activating endoplasmic reticulum stress-mediated apoptosis.

Methods

human breast cancer cell lines MCF-7 and T47D were used as research objects. MTT assay was used to detect the effect of Cel on cell viability. Western blotting were employed to detect the expression of apoptosis-related proteins. RT-qPCR and Western blotting were applied to measure the expression of endoplasmic reticulum stress-related molecules at mRNA and protein levels. A nude mouse model of orthotopic transplantation of MCF-7 cells was established to observe the effect of Cel on the growth of transplanted tumors.

Results

MTT Results showed that Cel inhibited the viability of MCF-7 and T47D cells in a dose-dependent manner (

0.05). Western blotting showed that Cel up-regulated the expression of apoptosis-related proteins

Cleaved PARP and BAX

and down-regulated the expression of BCL-2 (

0.05). RT-qPCR indicated that Cel up-regulated the mRNA levels of endoplasmic reticulum stress-related genes IRE1α

ATF6

PERK

ATF4

CHOP and BIP (

0.05). Western blotting revealed that Cel treatment resulted in increased expression levels of endoplasmic reticulum stress marker B

of PERK pathway related proteins p-PERK

p-eIF2α

ATF4 and CHOP

of IRE1α pathway associated proteins p-IRE1α and XBP1s

and of ATF6 pathway associated protein Cleared ATF6.

In vivo

experiment Results showed that Cel significantly reduced the volume of orthotopic transplanted tumor in nude mice (

0.05)

and had no significant effect on their body weight.

Conclusion

Cel has a certain inhibitory effect on the proliferation of ER

breast cancer MCF-7 and T47D cells

and its mechanism may be related to the activation of endoplasmic reticulum stress signaling pathway to induce apoptosis.

关键词

Keywords

references

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⁰

anti-ER+ breast cancer by activating endoplasmic reticulum stress to induce apoptosis

DOI：10.16016/j.2097-0927.202304042

摘要

Abstract

关键词

Keywords

references

anti-ER⁺ breast cancer by activating endoplasmic reticulum stress to induce apoptosis