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他莫昔芬诱导的内质网应激通过抑制 Wnt/β-连环蛋白信号通路促进乳腺癌 MDA-MB-231 细胞凋亡。

Tunicamycin-Induced Endoplasmic Reticulum Stress Promotes Breast Cancer Cell MDA-MB-231 Apoptosis through Inhibiting Wnt/-Catenin Signaling Pathway.

机构信息

Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Nanchang University, Nanchang, Jiangxi 330006, China.

Queen Mary University of London, Nanchang University, Nanchang, Jiangxi 330006, China.

出版信息

J Healthc Eng. 2021 Jul 15;2021:6394514. doi: 10.1155/2021/6394514. eCollection 2021.

DOI:10.1155/2021/6394514
PMID:34336161
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8298165/
Abstract

Triple negative breast cancer (TNBC) has significantly threatened human health. Many aspects of TNBC are closely related to Wnt/-catenin pathway, and cell apoptosis induced by endoplasmic reticulum stress (ER stress) in TNBC may act as a potential target of non-chemotherapy treatment. However, how ER stress interacts with this pathway in TNBC has not yet been understood. Here, the tunicamycin and LiCl have been applied to MDA-MB-231. The related proteins' expression was measured by western blotting. Moreover, acridine orange/ethidium bromide (AO/EB) staining was applied to test the apoptosis degree of the cells, and cell viability was tested by MTT experiment. Then, we found the ER stress and apoptosis degree of MDA-MB-231 were induced after treatment with tunicamycin. Besides, tunicamycin dose dependently inhibited both Wnt/-catenin pathway and cells viability. Licl, an activator of Wnt/-catenin signaling pathway, could significantly inhibit cell apoptosis. In conclusion, our study found that the activation of ER stress could promote the MDA-MB-231 apoptosis by repressing Wnt/-catenin pathway, which provides some promising prospects and basic mechanism to the further research.

摘要

三阴性乳腺癌(TNBC)严重威胁人类健康。TNBC 的许多方面都与 Wnt/-catenin 通路密切相关,内质网应激(ER 应激)诱导的 TNBC 细胞凋亡可能成为非化疗治疗的潜在靶点。然而,ER 应激与该通路在 TNBC 中的相互作用尚不清楚。本研究采用衣霉素和氯化锂(LiCl)处理 MDA-MB-231,通过 Western blot 检测相关蛋白的表达。此外,通过吖啶橙/溴化乙锭(AO/EB)染色检测细胞凋亡程度,通过 MTT 实验检测细胞活力。结果发现,衣霉素处理后 MDA-MB-231 的 ER 应激和凋亡程度增加,且衣霉素呈剂量依赖性抑制 Wnt/-catenin 通路和细胞活力。Wnt/-catenin 信号通路的激活剂 LiCl 可显著抑制细胞凋亡。综上,本研究发现 ER 应激的激活可通过抑制 Wnt/-catenin 通路促进 MDA-MB-231 细胞凋亡,为进一步研究提供了有前景的前景和基础机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9846/8298165/b0c9ba2ed3eb/JHE2021-6394514.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9846/8298165/f3c19b6602ad/JHE2021-6394514.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9846/8298165/c1e8036d54d5/JHE2021-6394514.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9846/8298165/7c1aff75f53b/JHE2021-6394514.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9846/8298165/b0c9ba2ed3eb/JHE2021-6394514.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9846/8298165/f3c19b6602ad/JHE2021-6394514.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9846/8298165/c1e8036d54d5/JHE2021-6394514.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9846/8298165/7c1aff75f53b/JHE2021-6394514.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9846/8298165/b0c9ba2ed3eb/JHE2021-6394514.004.jpg

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