人参皂苷 Rh2 及其辛酯衍生物通过 c-Jun/COX2/PGE2 通路抑制肝癌的侵袭和转移。
Ginsenoside Rh2 and its octyl ester derivative inhibited invasion and metastasis of hepatocellular carcinoma via the c-Jun/COX2/PGE2 pathway.
机构信息
State Key Laboratory of Food Science and Resources, College of Food Science, Nanchang University, Nanjing East Road, Nanchang, Jiangxi 330047, China.
Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Bayi Avenue, Nanchang, Jiangxi 330000, China.
出版信息
Phytomedicine. 2023 Dec;121:155131. doi: 10.1016/j.phymed.2023.155131. Epub 2023 Oct 6.
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.
背景
肝癌是一个全球性的医学难题。肝癌的治疗面临着高复发率和侵袭性的巨大挑战。因此，针对环氧合酶 2（COX2）/前列腺素 E2（PGE2）通路诱导的上皮-间充质转化（EMT）的治疗策略已经成为研究热点。人参皂苷 Rh2 已被证明能抑制 EMT。然而，其潜在机制尚不清楚。此外，我们之前的研究表明，Rh2 的辛酯衍生物（Rh2-O）比 Rh2 具有更好的抗增殖和免疫调节作用，这表明 Rh2-O 可能也对侵袭和转移具有抑制作用。
目的
本研究旨在探讨 Rh2 和 Rh2-O 对肝癌侵袭和转移的抑制作用，并研究这些作用是否依赖于 c-Jun/COX2/PGE2 通路。
研究设计
用 Rh2 和 Rh2-O 处理 Huh-7 肝癌细胞和 H22 荷瘤小鼠。
方法
本文通过划痕愈合实验、Transwell 实验和荷瘤小鼠实验，检测 Rh2 和 Rh2-O 对侵袭和转移的抑制作用，并通过外源性 PGE2、COX2 激活和 c-Jun 过表达来验证 c-Jun/COX2/PGE2 通路的参与。
结果
结果表明，Rh2 和 Rh2-O 能以剂量依赖性方式有效抑制侵袭和转移（p<0.05），且 Rh2-O 的作用强于 Rh2。此外，外源性 PGE2、外源性 LPS 激活 COX2 和转染过表达 c-Jun 均能逆转 Rh2 和 Rh2-O 对转移或 EMT 的抑制作用（p<0.05）。
结论
Rh2 和 Rh2-O 可通过抑制 c-Jun/COX2/PGE2 通路介导的 EMT 抑制肝癌的侵袭和转移。
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