Anhydroicaritin Inhibits EMT in Breast Cancer by Enhancing GPX1 Expression: A Research Based on Sequencing Technologies and Bioinformatics Analysis

• DOI: 10.3389/fcell.2021.764481
• Publication Date: 2022-02-01T05:55:37Z
• Authors: Feifei Li; Youyang Shi; Xiaojuan Yang; Zhanyang Luo; Guangtao Zhang; Kui Yu; Feng Li; Lixin Chen; Youkang Zhao; Ying Xie; Yuanyuan Wu; Jianfeng Yang; Xiqiu Zhou; Sheng Liu
• Keywords: GPX1

Background: Breast cancer (BC) is the leading cause of cancer-related deaths among women worldwide. The application advanced technology has promoted accurate diagnosis and treatment cancer. Anhydroicaritin (AHI) a flavonoid with therapeutic potential in BC treatment. current study aimed to determine AHI's mechanism via RNA sequencing, comprehensive bioinformatics analysis, experimental verification. Methods: Network pharmacology MTT (3-(4,5)-dimethylthiazolyl-3,5- diphenyltetrazolium bromide) experiments were conducted first confirm anti-BC effect. sequencing was performed identify genes affected by AHI. Differential expression survival gene set enrichment immune infiltration analysis analysis. Western blot reverse transcription-polymerase chain reaction (RT-PCR) experiment, molecular docking, drug affinity responsive target stability (DARTS) also direct effect on glutathione peroxidase 1 (GPX1) expression. Confocal immunofluorescence verify occurrence development epithelial-mesenchymal transition (EMT). Finally, nude mouse xenografts established, explored. Results: results demonstrated that targets related proliferation, invasion, metastasis cells. AHI significantly inhibited proliferation 4T1 MDA-MB-231 cells experiments. showed upregulated GPX1 Next, revealed less expressed than normal breast tissues. Patients high levels tended have prolonged overall disease-free patients low BC. RT-PCR increased protein mRNA GPX1. Molecular docking DARTS confirmed binding combination between After evaluation EMT scores 1,078 BC, we found role possibly suppression malignant EMT. confocal E-cadherin reduced vimentin Animal tumor growth. enhancing caspase3 cleavage, hence inhibiting markers (i.e., N-cadherin vimentin) Ki-67. Conclusion: plays critical which may be biomarker for prognosis. In addition, suppressed increasing expression, serve as therapy