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. 2025 Feb;105(2):e70063.
doi: 10.1111/cbdd.70063.

Baicalein Inhibits Tumor Property of Hepatocellular Carcinoma Cells Through the Inactivation of the E2F Transcription Factor 1/Mediator Complex Subunit 7 Axis

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Baicalein Inhibits Tumor Property of Hepatocellular Carcinoma Cells Through the Inactivation of the E2F Transcription Factor 1/Mediator Complex Subunit 7 Axis

Pinghui Song et al. Chem Biol Drug Des. 2025 Feb.

Abstract

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis. Baicalein, a natural compound, can regulate multiple cellular processes in various cancer types. In this study, we investigated the role of baicalein in regulating HCC and explored its potential mechanism. The expression of mediator complex subunit 7 (MED7) and E2F transcription factor 1 (E2F1) was analyzed by quantitative real-time polymerase chain reaction or Western blotting assay. Cell proliferation was assessed by cell colony formation assay and 5-ethynyl-2'-deoxyuridine assay. Cell migration was analyzed by transwell assay and wound-healing assay. Cell invasion was analyzed by transwell assay. Angiogenic ability of HCC cells was assessed by tube formation assay. Dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to validate the association between E2F1 and MED7. The xenograft mouse model assay was conducted to determine the effects of baicalein and E2F1 overexpression on tumor formation. Immunohistochemistry assay was used to determine positive expression rates of proteins. Upregulation of MED7 and E2F1 expression was observed in both HCC tissues and cells. Knockdown of MED7 suppressed HCC cell proliferation, migration, invasion, and tube formation. Transcriptional activation of MED7 by E2F1 was demonstrated in HCC cells. Overexpression of MED7 mitigated the effects induced by E2F1 depletion in HCC cells. Additionally, baicalein treatment effectively inhibited the tumor property of HCC cells by decreasing E2F1 expression in both in vitro and in vivo models. Baicalein inhibited the tumor property of HCC cells through the inactivation of the E2F1/MED7 axis, highlighting its potential clinical application in the treatment of HCC.

Keywords: E2F1; MED7; baicalein; hepatocellular carcinoma.

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