Natural triterpenoid saponin Momordin Ic suppresses HepG2 cell invasion via COX-2 inhibition and PPARγ activation
Natural triterpenoid saponin Momordin Ic suppresses HepG2 cell invasion via COX-2 inhibition and PPARγ activation
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天然三萜皂苷 Momordin Ic 通过 COX-2 抑制和 PPARγ 激活抑制 HepG2 细胞侵袭
DOI：
10.1016/j.tiv.2020.104784
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发表时间：
2020
影响因子：
3.2
通讯作者：
Xuebo Liu
中科院分区：
文献类型：
--
作者：
Jing Wang;Ying Han;Man Wang;Qianqian Zhao;Xuefeng Chen;Xuebo Liu
我们以前报道过从地肤果实中提取的天然三萜皂苷--苦瓜素Ic（MomordinIc）。施拉德，部分通过改变E-cadherin、VCAM-1、ICAM-1和MMP-9发挥抗肝癌侵袭作用。JNK和p38-MAPK通路在一定程度上改变了这四种分子。然而，MMP-9，这是大大抑制了苦瓜素Ic，既不影响p38-MAPK和JNK。因此，我们进一步研究了以前发现的调节细胞生长的其他信号，如考克斯-2和过氧化物酶体增殖物激活受体γ，如何在细胞侵袭过程中发挥作用。结果表明，考克斯-2和过氧化物酶体增殖物激活受体γ在苦瓜素抑制细胞侵袭中起重要作用。而考克斯-2仅调节E-cadherin和ICAM-1。PPARγ不参与VCAM-1的表达，但对其他蛋白的表达有显著影响。Akt是考克斯-2和过氧化物酶体增殖物激活受体γ上游的激酶，它不影响ICAM-1的表达，但直接介导E-cadherin、VCAM-1和MMP-9的表达。Momordin Ic通过激活PPARγ和抑制考克斯-2抑制HepG 2细胞侵袭。这些结果为苦瓜素Ic的抗侵袭机制提供了依据。
We previously reported that Momordin Ic, a natural triterpenoid saponin from the fruit ofKochia scoparia(L.) Schrad., exerts good anti-invasive activity on liver cancer partly by altering E-cadherin, VCAM-1, ICAM-1 and MMP-9. The JNK and p38-MAPK pathways differentially altered the four molecules to some extent. However, MMP-9, which is greatly suppressed by Momordin Ic, was affected by neither p38-MAPK nor JNK. Therefore, we further investigated how other signals previously found to regulate cell growth, such as COX-2 and PPARγ, function in the process of cell invasion by western blot. The results demonstrated that COX-2 and PPARγ play a significant role in Momordin Ic-inhibited cell invasion. However, COX-2 only regulated E-cadherin and ICAM-1. PPARγ was not involved in VCAM-1alteration but was significant for the expressions of other proteins. Akt, a kinase upstream of COX-2 and PPARγ, did not influence ICAM-1 but directly mediated the expression of E-cadherin, VCAM-1 and MMP-9. Momordin Ic weakens HepG2 cell invasion through PPARγ activation and COX-2 inhibition. These findings provide evidence for the anti-invasion mechanism of Momordin Ic.