miR ‐3,178 contributes to the therapeutic action of baicalein against hepatocellular carcinoma cells via modulating HDAC10

黄芩素 癌症研究 细胞生长 细胞凋亡 细胞周期 蛋白激酶B 化学 医学 药理学 生物化学
作者
Jun'an Qi,Jun Li,Beibei Bie,Mengjiao Shi,Mengchen Zhu,Jing Tian,Kai Zhu,Jin Sun,Yanhua Mu,Zongfang Li,Ying Guo
出处
期刊:Phytotherapy Research [Wiley]
卷期号:37 (1): 295-309 被引量:13
标识
DOI:10.1002/ptr.7613
摘要

Hepatocellular carcinoma (HCC) is the most common type of hepatic malignancies with high mortality and poor prognosis. Baicalein, one of the major and bioactive flavonoids isolated from Scutellaria baicalensis Georgi, which is reported to have anti-proliferation effect in varying cancers, including HCC, whose underlying molecular mechanism is still largely unknown. In this study, we found that baicalein significantly inhibited proliferation and colony formation, blocked cell cycle, and promoted apoptosis in HCC cells MHCC-97H and SMMC-7721 in vitro and reduced tumor volume and weight in vivo. Increased microRNA (miR)-3,178 levels and decreased histone deacetylase 10 (HDAC10) expression were found in cells treated with baicalein and in patients' HCC tissues. HDAC10 was identified as a target gene of miR-3,178 by luciferase activity and western blot. Both baicalein treatment and overexpression of miR-3,178 could downregulate HDAC10 protein expression and inactivated AKT, MDM2/p53/Bcl2/Bax and FoxO3α/p27/CDK2/Cyclin E1 signal pathways. Not only that, knockdown of miR-3,178 could partly abolish the effects of baicalein and the restoration of HDAC10 could abated miR-3,178-mediated role in HCC cells. Collectively, baicalein inhibits cell viability, blocks cell cycle, and induces apoptosis in HCC cells by regulating the miR-3,178/HDAC10 pathway. This finding indicated that baicalein might be promising for treatment of HCC.
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