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穿心莲内酯通过抑制NF-κB/miR-21-5p/PDCD4信号通路抑制腔面型乳腺癌的生长和转移。

Andrographolide Suppresses the Growth and Metastasis of Luminal-Like Breast Cancer by Inhibiting the NF-κB/miR-21-5p/PDCD4 Signaling Pathway.

作者信息

Li Junchen, Huang Lixun, He Zinan, Chen Minggui, Ding Yi, Yao Yuying, Duan Youfa, Zixuan Li, Qi Cuiling, Zheng Lingyun, Li Jiangchao, Zhang Rongxin, Li Xiaoming, Dai Jianwei, Wang Lijing, Zhang Qian-Qian

机构信息

School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.

Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, China.

出版信息

Front Cell Dev Biol. 2021 Jun 23;9:643525. doi: 10.3389/fcell.2021.643525. eCollection 2021.

Abstract

Tumor growth and metastasis are responsible for breast cancer-related mortality. Andrographolide (Andro) is a traditional anti-inflammatory drug used in the clinic that inhibits NF-κB activation. Recently, Andro has been found in the treatment of various cancers. Andro inhibits breast cell proliferation and invasion and induces apoptosis activating various signaling pathways. Therefore, the underlying mechanisms with regard to the antitumor effects of Andro still need to be further confirmed. Herein, a MMTV-PyMT spontaneous luminal-like breast cancer lung metastatic transgenic tumor model was employed to estimate the antitumor effects of Andro on breast cancer . Andro significantly inhibited tumor growth and metastasis in MMTV-PyMT mice and suppressed the cell proliferation, migration, and invasion of MCF-7 breast cancer cells . Meanwhile, Andro significantly inhibited the expression of NF-κB, and the downregulated NF-κB reduced miR-21-5p expression. In addition, miR-21-5p dramatically inhibited the target gene expression of programmed cell death protein 4 (PDCD4). In the current study, we demonstrated the potential anticancer effects of Andro on luminal-like breast cancer and indicated that Andro inhibits the expression of miR-21-5p and further promotes PDCD4 NF-κB suppression. Therefore, Andro could be an antitumor agent for the treatment of luminal-like breast cancer in the clinic.

摘要

肿瘤生长和转移是乳腺癌相关死亡的原因。穿心莲内酯(Andro)是一种临床上使用的传统抗炎药物,可抑制核因子κB(NF-κB)的激活。最近,已发现穿心莲内酯可用于治疗多种癌症。穿心莲内酯抑制乳腺细胞增殖和侵袭,并通过激活各种信号通路诱导细胞凋亡。因此,穿心莲内酯抗肿瘤作用的潜在机制仍需进一步证实。在此,采用MMTV-PyMT自发管腔样乳腺癌肺转移转基因肿瘤模型来评估穿心莲内酯对乳腺癌的抗肿瘤作用。穿心莲内酯显著抑制MMTV-PyMT小鼠的肿瘤生长和转移,并抑制MCF-7乳腺癌细胞的增殖、迁移和侵袭。同时,穿心莲内酯显著抑制NF-κB的表达,而下调的NF-κB降低了miR-21-5p的表达。此外,miR-21-5p显著抑制程序性细胞死亡蛋白4(PDCD4)的靶基因表达。在本研究中,我们证明了穿心莲内酯对管腔样乳腺癌的潜在抗癌作用,并表明穿心莲内酯抑制miR-21-5p的表达,并通过抑制NF-κB进一步促进PDCD4的表达。因此,穿心莲内酯可能成为临床上治疗管腔样乳腺癌的一种抗肿瘤药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b6e/8261247/8ae6c867ce15/fcell-09-643525-g001.jpg

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