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

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.

Automated summary

Baicalin, derived from Scutellaria baicalensis Georgi, has been found to inhibit hepatocellular carcinoma (HCC) growth and metastasis. This study showed that Baicalin suppressed HCC cell proliferation, invasion, and metastasis, induced cell cycle arrest and apoptosis. In vivo experiments demonstrated that Baicalin inhibited HCC growth. Mechanistically, Baicalin inhibited the expressions of ROCK1, p-GSK-3β, and β-catenin, while up-regulating GSK-3β and p-β-catenin expressions. Baicalin also regulated the expressions of various proteins involved in HCC progression. Molecular docking studies revealed a binding interaction between Baicalin and ROCK1. Suppression of ROCK1 expression enhanced the inhibitory effects of Baicalin on HCC, while restoration of ROCK1 expression reduced Baicalin's efficacy. These findings suggest that Baicalin suppresses HCC proliferation and metastasis through the ROCK1/GSK-3β/β-catenin signaling pathway.