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Actinidia chinensis Planch root extract (acRoots) inhibits hepatocellular carcinoma progression by inhibiting EP3
Tingting Fang1, Jiayun Hou2, Mingyan He1
1Liver Cancer Institute, Zhongshan Hospital, Shanghai, China.
Abstract:
A wide range of studies has demonstrated the potent anticancer activity of Chinese herbs. Here, we evaluated the anticancer activity and molecular mechanisms of Actinidia chinensis root extract (acRoots) on hepatocellular carcinoma (HCC). HepG2 HCC cells were treated with various concentrations of acRoots for 72 h and examined by mRNA expression profiling, revealing alterations in cellular immunity, inflammation, proliferation, cell cycle, and metabolic signaling responses. Further analysis of the altered genes in cellular immunity and inflammation gene clusters identified prostaglandin E receptor 3 (EP3) as a key regulator of gene expression in response to acRoots. Further analysis revealed inhibition of cell growth, migration, and invasion in HCC in response to acRoots, along with increased apoptosis due to downregulation of EP3 expression. Treatment with acRoots and EP3 antagonist L-798106 led to decreases in VEGF, EGFR, MMP2, and MMP9 expression in HCC cells, along with significant effects on growth, migration, invasion, and apoptosis; the effects were reversed/blocked by the EP3 agonist sulprostone. Taken together, these data clearly demonstrated that acRoots inhibit HCC cell invasion and metastasis via inhibition of EP3 expression, resulting in decreased activation of VEGF, EGFR, MMP2, and MMP9.
Insights
Chinese herb extract (acRoots) from Actinidia chinensis root inhibits hepatocellular carcinoma (HCC) cell growth and metastasis. It works by downregulating prostaglandin E receptor 3 (EP3) expression, impacting key cancer-related genes.
Area of Science:
- Oncology
- Pharmacology
- Natural Products
Background:
- Chinese herbs show significant anticancer potential.
- Hepatocellular carcinoma (HCC) remains a major global health concern.
- Targeting molecular pathways is crucial for effective HCC treatment.
Purpose of the Study:
- To investigate the anticancer effects of Actinidia chinensis root extract (acRoots) on HCC.
- To elucidate the molecular mechanisms underlying acRoots' action in HCC.
- To identify key molecular targets for acRoots' therapeutic activity.
Main Methods:
- HepG2 HCC cells were treated with acRoots.
- mRNA expression profiling was used to analyze gene expression changes.
- The role of prostaglandin E receptor 3 (EP3) was investigated.
- Effects on cell growth, migration, invasion, and apoptosis were assessed.
Main Results:
- acRoots altered genes involved in immunity, inflammation, proliferation, cell cycle, and metabolism.
- EP3 was identified as a key regulator of acRoots' effects.
- acRoots inhibited HCC cell growth, migration, and invasion, increasing apoptosis via EP3 downregulation.
- acRoots decreased VEGF, EGFR, MMP2, and MMP9 expression, effects mediated by EP3.
Conclusions:
- acRoots exhibit potent anticancer activity against HCC.
- The mechanism involves the downregulation of EP3 expression.
- This leads to the inhibition of HCC cell invasion and metastasis by reducing VEGF, EGFR, MMP2, and MMP9 activation.
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