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Abstract Title:

Wogonin Restrains the Malignant Progression of Lung Cancer through Modulating MMP1 and PI3K/AKT Signaling Pathway.

Abstract Source:

Protein Pept Lett. 2022 Oct 27. Epub 2022 Oct 27. PMID: 36305146

Abstract Author(s):

Junhao Guo, Yanjing Hu, Gang Jin, Zhi Zhao, Fangyuan Nan, Xin Hu, Yunsheng Hu, Qun Han

Article Affiliation:

Junhao Guo

Abstract:

BACKGROUND: Wogonin, a natural flavonoid compound, represses cancer cell growth and induces cancer cell apoptosis in diverse malignancies. However, the function of Wogonin in lung cancer cells and its regulatory mechanism deserve to be identified.

METHODS: A549 and H460 cells were treated with Wogonin, and the cell growth, apoptosis, migration and invasion were measured by CCK-8 and EdU, flow cytometry and Transwell assays. The targeted genes of Wogonin and lung cancer were identified from the TCMSP database and Genecards database, respectively. The STRING database and Cytoscape software were used to establish a PPI network and screen hub genes. GO and KEGG analysis were conducted to explore the functions and signal pathway related to the hub genes. MMP1 expression in lung cancer was analyzed using the UALCAN databases, and GSEA was performed utilizing LinkedOmics. Gelatin zymography assay was used to detect MMP1 activity. MMP1 mRMA expression was detected by qRT-PCR. Besides, MMP1, p-AKT and c-Myc protein were detected by Western Blot assay.

RESULTS: Wogonin could suppress the proliferation, migration and invasion of A549 and H460 cells, and induce the apoptosis. GO and KEGG enrichment analysis revealed the hub genes were mostly enriched in re-entry into mitotic cell cycle and apoptosis. The expression of MMP1 was markedly up-regulated in lung squamous cell carcinoma and lung adenocarcinoma tissues, as well as lung cancer cell lines. Wogonin could significantly inhibit MMP1 expression and activity, and overexpression of MMP1 significantly reversed the effect of Wogonin on the malignant phenotypes of A549 and H460 cells. Wogonin inhibited the expression of p-AKT and c-Myc protein by regulating MMP1.

CONCLUSION: Wogonin can repress the growth, metastatic potential of lung cancer cells, and promote cell apoptosis via repressing MMP1 expression and modulating PI3K/AKT signaling pathway.

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