Exploration of the Potential Mechanism of Tao Hong Si Wu Decoction for the Treatment of Breast Cancer Based on Network Pharmacology and In Vitro Experimental Verification.

Ni Wang,Yongzhong Wang,Furui Chu,Xianchun Duan,Lingyu Pan,Changyi Fei,Daiyin Peng,Yan Chen,Shi Huang

doi:10.3389/fonc.2021.731522

Ni Wang, Yongzhong Wang + Show 7 more

Open Access

https://doi.org/10.3389/fonc.2021.731522

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Abstract

BackgroundTao Hong Si Wu Decoction (THSWD) is a well-known traditional Chinese medicine used clinically alone or combined with drugs to treat breast cancer. However, there has been no study to date on the underlying mechanisms of its therapeutic effects.ObjectivesTo explore the potential mechanism of THSWD for the treatment of breast cancer using network pharmacology and experimental research.MethodsThe active ingredients of THSWD were screened according to Lipinski’s rule of five based on the 107 ingredients of THSWD identified by UPLC-Q-TOF-MSE. The targets of THSWD and breast cancer from multiple databases were collected, and a Compound-Target-Pathway network based on protein-protein interaction (PPI) was constructed. Gene ontology (GO) analysis and KEGG pathway analysis were performed via the DAVID server. Molecular docking studies verified the selected key ingredients and key targets. The results of network pharmacology were verified by in vitro experiments. Including the effects of THSWD drug-containing rat serum (THSWD serum) on cell proliferation, and on the targets HRAS, MAPK1, AKT1, GRB2, and MAPK14 were assayed by RT-qPCR and Western blot assays.ResultsIn total, 27 active ingredients including 8 core components, were obtained from 107 ingredients and 218 THSWD target genes for the treatment of breast cancer were identified. THSWD is active in the treatment of breast cancer by targeting Ras, FoxO, PI3K-Akt and other signaling pathways. MCF-7 and MDA-MB-231 cell proliferation was inhibited by THSWD serum in a time and concentration dependent manner. THSWD could regulated the RNA and protein expression of core targets HRAS, MAPK1, AKT1, GRB2, and MAPK14 for treatment of breast cancer.ConclusionThe results of network pharmacology study showed that THSWD is active against breast cancer by intervening with multiple targets and pathways. Luteolin, kaempferol, senkyunolide E, and other 8 compounds may be the core active ingredients of THSWD in the treatment of breast cancer. THSWD treatment of breast cancer may be related to targeting Ras, FoxO, PI3K-Akt, and other signal pathways associated with the core targets HRAS, MAPK1, AKT1, GRB2, and MAPK14.

Highlights

The latest data from the International Agency for Research on Cancer (IARC) survey showed that Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%) in 2018 [1]
In OMIM and Genecard databases, 3264 repetitive breast cancer-related targets were obtained, the 461 targets predicted with the active ingredients of Tao Hong Si Wu Decoction (THSWD) were intersected using a Venn diagram, resulting in 218 intersection targets, which were potential active targets of THSWD acting on breast cancer (Figure 1)
Most of the docked targets were distributed in pathways involving cancer, such as Ras, FoxO, PI3K-Akt, and other signaling pathways, demonstrating that the active ingredients of THSWD could have an impact on the occurrence and development of breast cancer by acting on the related targets and their corresponding signaling pathways

Summary

Introduction

The latest data from the International Agency for Research on Cancer (IARC) survey showed that Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%) in 2018 [1]. Epidemiological data across Chinese cancer centers in 2019 showed that the incidence and mortality rates of breast cancer were first and fifth among female malignant tumors, respectively, and both rates have shown a rising trend. The most common clinical treatment interventions are surgical resection, radiotherapy, and chemotherapy, but surgical resection does not improve prognosis, while long-term radiotherapy and chemotherapy can cause serious side effects. Studies have shown that the combined treatment with traditional Chinese medicine (TCM) can improve the quality of life of breast cancer patients [2]. Tao Hong Si Wu Decoction (THSWD) is a well-known traditional Chinese medicine used clinically alone or combined with drugs to treat breast cancer. There has been no study to date on the underlying mechanisms of its therapeutic effects

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