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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Mechanism of Erianin anti-triple negative breast cancer based on transcriptomics methods and network pharmacology
Ming Li1, Yuan Zhao2, Huimin Li1
1Laboratory of Molecular Genetics of Aging and Tumour, Medical School, Kunming University of Science and Technology, Chenggong Campus, Kunming, Yunnan 650500, China.
Abstract:
Triple negative breast cancer (TNBC) is a highly aggressive illness that lacks effective targeted treatments. Although Erianin has shown potential antitumor properties, its precise mechanism of action and target in TNBC remain unclear, hampering the development of drugs. The present study investigated the underlying mechanism of action of Erianin in treating TNBC by using transcriptomics and network pharmacology approaches. We evaluated Erianin's bioactivity in TNBC cell lines and xenograft tumor models. The results showed that Erianin significantly inhibited TNBC cell proliferation and impeded tumor growth. A subsequent analysis of transcriptomic and network pharmacological data identified 51 mutual targets. Analysis of protein-protein interactions identified eight hub targets. Furthermore, molecular docking indicated that the PPARA binding energy was the lowest for Erianin among the hub targets, followed by ROCK2, PDGFRB, CCND1, MUC1, and CDK1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the common targets were associated with multiple cancer-related signaling pathways, including focal adhesion, PI3K-Akt signaling pathway, Rap1 signaling pathway, microRNAs in cancer, and human papillomavirus infection. The results of the Western blot and immunohistochemistry experiment further showed that Erianin could suppress PI3K/Akt signaling pathway activation. After co-incubation with SC79, the cell inhibition rate of Erianin was decreased, which further confirmed that Erianin inhibits TNBC progression via the PI3K-AKT signaling pathway. In conclusion, our results indicated that Erianin has the potential to inhibit the proliferation of TNBC by downregulating the PI3K/AKT signaling pathway by transcriptomics and network pharmacology. Therefore, Erianin appears to be a promising compound for the effective treatment of TNBC.
Insights
Erianin effectively inhibits triple negative breast cancer (TNBC) proliferation and tumor growth by downregulating the PI3K/AKT signaling pathway, offering a promising new treatment avenue.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Triple negative breast cancer (TNBC) is an aggressive cancer subtype lacking targeted therapies.
- Erianin exhibits potential antitumor activity, but its mechanism in TNBC is not fully understood.
Purpose of the Study:
- To elucidate the mechanism of action of Erianin in TNBC using transcriptomics and network pharmacology.
- To identify key molecular targets and pathways affected by Erianin in TNBC.
Main Methods:
- Transcriptomics and network pharmacology were employed to identify Erianin's targets.
- In vitro TNBC cell lines and in vivo xenograft models were used for bioactivity evaluation.
- Molecular docking and Western blot analyses were performed to validate targets and pathways.
Main Results:
- Erianin significantly inhibited TNBC cell proliferation and tumor growth.
- Fifty-one mutual targets were identified, with eight hub targets highlighted, including PPARA and ROCK2.
- Erianin was found to suppress the PI3K/Akt signaling pathway, confirmed by Western blot and SC79 co-incubation experiments.
Conclusions:
- Erianin demonstrates therapeutic potential for TNBC by inhibiting proliferation and tumor growth.
- The PI3K/AKT signaling pathway is a key mediator of Erianin's anti-TNBC effects.
- Erianin represents a promising candidate for novel TNBC drug development.
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