Baicalin inhibits hepatocellular carcinoma cell growth and metastasis by suppressing ROCK1 signaling

被引:14
|
作者
Sun, Jialing [1 ,2 ]
Yang, Xuemei [3 ]
Sun, Haitao [1 ,4 ]
Huang, Shaohui [4 ]
An, Haiyan [4 ]
Xu, Wei [4 ]
Chen, Weicong [4 ]
Zhao, Wenting [4 ]
He, Chunyu [4 ]
Zhong, Xiaodan [4 ]
Li, Tong [4 ]
Liu, Yang [4 ]
Wen, Bin [6 ]
Du, Qingfeng [4 ,5 ,7 ]
He, Songqi [1 ,4 ,7 ,8 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China
[2] Guangzhou Univ Chinese Med, Shenzhen Tradit Chinese Med Hosp, Clin Med Coll 4, Dept Hepatol, Shenzhen, Guangdong, Peoples R China
[3] Southern Med Univ, Affiliated Zhuhai Hosp, Zhuhai Hosp Integrated Tradit Chinese & Western Me, Zhuhai, Guangdong, Peoples R China
[4] Southern Med Univ, Sch Tradit Chinese Med, Guangzhou, Guangdong, Peoples R China
[5] Air Force Hosp Southern Theater Command, Dept Tradit Chinese Med, Guangzhou, Guangdong, Peoples R China
[6] Air Force Hosp Southern Theater Command, Dept Tradit Chinese Med, Guangzhou 510602, Guangdong, Peoples R China
[7] Southern Med Univ, Sch Tradit Chinese Med, Guangzhou 510515, Guangdong, Peoples R China
[8] Nanfang Hosp, Guangzhou 510515, Guangdong, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
Baicalin; growth; hepatocellular carcinoma; metastasis; ROCK1/GSK; 3; beta/beta; catenin signaling pathway; PROLIFERATION; INVASION; KINASE;
D O I
10.1002/ptr.7873
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Hepatocellular carcinoma (HCC) is a common malignancy affecting many people worldwide. Baicalin is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi. It can effectively inhibit the occurrence and development of HCC. Nonetheless, the mechanism through which Baicalin inhibits HCC growth and metastasis remain unknown. This work discovered that Baicalin inhibited HCC cell proliferation, invasion, metastasis while inducing cell cycle arrest at the G0/G1 phase and apoptosis. In vivo HCC xenograft results indicated that Baicalin inhibited HCC growth. Western blotting analysis indicated that Baicalin suppressed the expressions of ROCK1, p-GSK-3 ss, and ss-catenin, whereas it up-regulated the expressions of GSK-3 ss and p-ss-catenin. Baicalin also reduced the expressions of Bcl-2, C-myc, Cyclin D1, MMP-9, and VEGFA, while increasing the expression of Bax. Molecular docking revealed that Baicalin docked in the binding site of the ROCK1 agonist, with a binding energy of -9 kcal/mol between the two. In addition, lentivirus-mediated suppression of ROCK1 expression improved the inhibitory effect of Baicalin on the proliferation, invasion, and metastasis of HCC and the expression of proteins associated with ROCK1/GSK-3 ss/ss-catenin signaling pathway. Moreover, restoring ROCK1 expression decreased the anti-HCC efficacy of Baicalin. These findings suggest that Baicalin may decrease HCC proliferation and metastasis by suppressing ROCK1/ GSK-3 ss/ss-catenin signaling.
引用
收藏
页码:4117 / 4132
页数:16
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