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

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

doi:10.3389/fcell.2021.643525

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

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

Authors

Junchen Li¹, Lixun Huang¹, Zinan He¹, Minggui Chen¹, Yi Ding^{1

2}, Yuying Yao¹, Youfa Duan¹, Li Zixuan¹, Cuiling Qi^{1

2}, Lingyun Zheng^{1

2}, Jiangchao Li^{1

2}, Rongxin Zhang^{1

2}, Xiaoming Li³, Jianwei Dai^{4

5

6}, Lijing Wang^{1

2}, Qian-Qian Zhang^{1

2}

Affiliations

¹ School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
² Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, China.
³ Department of Pathology, People's Hospital of Baoan District, Affiliated Baoan Hospital of Shenzhen, Southern Medical University, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China.
⁴ Guangzhou Medical University-Guangzhou Institute of Biomedicine and Health (GMU-GIBH) Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
⁵ Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁶ The State Key Lab of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

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 via 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 in vivo. 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 in vitro. 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 via NF-κB suppression. Therefore, Andro could be an antitumor agent for the treatment of luminal-like breast cancer in the clinic.

Keywords: NF-κB/miR-21-5p/PDCD4 signaling pathway; andrographolide; growth; luminal-like breast cancer; metastasis.