Journal
PHYTOMEDICINE
Volume 121, Issue -, Pages -Publisher
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2023.155131
Keywords
Invasion; Metastasis; Epithelial-mesenchymal transition; Ginsenoside Rh2; Derivatives of ginsenoside; Hepatocellular carcinoma; C-Jun/COX2/ PGE2 pathway
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This study investigated the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis of hepatocellular carcinoma, and revealed that these effects were mediated by the c-Jun/COX2/PGE2 pathway. Rh2-O showed stronger effects compared to Rh2.
Background: Liver cancer is a topical global health issue. The treatment of liver cancer meets significant challenges in the high recurrence rate and invasive incidence. Therefore, the treatment strategies that target epithelial-mesenchymal transition (EMT) induced by cyclooxygenase 2 (COX2)/ prostaglandin E2 (PGE2) pathway have become epidemic. Ginsenoside Rh2 has been proved to inhibit the EMT. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited superior anti-proliferative and immunomodulatory effects than Rh2 in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on invasion and metastasis. Purpose: The aim of current study is to explore the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis of hepatocellular carcinoma, and to investigate whether these effects are dependent on the c-Jun/COX2/PGE2 pathway. Study Design: The Huh-7 liver cancer cells and the H22 tumor-bearing mice were treated with Rh2 and Rh2-O.Method: In this paper, the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis were tested by wound healing, trans-well assay and tumor-bearing mice, and the involvement of c-Jun/COX2/PGE2 pathway were verified by exogenous PGE2, activation of COX2 and overexpression of c-Jun. Results: The results showed that Rh2 and Rh2-O could efficiently inhibit the invasion and metastasis in a dose-dependent manner (p < 0.05). And the Rh2-O showed stronger effects than Rh2. Moreover, the exogenous PGE2, activation of COX2 by exogenous LPS and the overexpression of c-Jun by transfection all reversed the inhibitory effects of Rh2 and Rh2-O on metastasis or EMT (p < 0.05). Conclusion: Rh2 and Rh2-O could inhibit the invasion and metastasis of hepatocellular carcinoma via restraining the EMT, which was mediated by c-Jun/COX2/PGE2 pathway.
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