Suppressive effects of Momordin Ic on HepG2 cell migration and invasion by regulating MMP-9 and adhesion molecules: Involvement of p38 and JNK pathways
Suppressive effects of Momordin Ic on HepG2 cell migration and invasion by regulating MMP-9 and adhesion molecules: Involvement of p38 and JNK pathways
复制标题
Momordin Ic 通过调节 MMP-9 和粘附分子对 HepG2 细胞迁移和侵袭的抑制作用：p38 和 JNK 通路的参与
DOI：
10.1016/j.tiv.2019.01.007
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发表时间：
2019
影响因子：
3.2
通讯作者：
Liu Xuebo
中科院分区：
文献类型：
--
作者：
Wang Jing;Liu Qian;Xiao Haifang;Luo Xingxing;Liu Xuebo
Momordin Ic以前被发现诱导肝癌细胞凋亡和自噬。为了进一步阐明苦瓜素Ic的抗癌活性，我们分析了苦瓜素Ic对细胞迁移和侵袭的抑制作用。我们还研究了与MMP-9、粘附分子和信号转导相关的机制。结果表明，苦瓜素Ic有效地阻止了细胞的粘附、迁移和侵袭。E-cadherin介导的同型粘附被诱导，而VCAM-1、ICAM-1和MMP-9被抑制。苦瓜素Ic影响p38、JNK和Erk与VEGF的磷酸化。p38可有效调节E-cadherin、VCAM-1和ICAM-1的表达。JNK对E-cadherin的改变起重要作用。尽管Momordin Ic可降低Erk的磷酸化水平，但Erk几乎不改变E-cadherin、VCAM-1、ICAM-1和MMP-9。这些结果表明，苦瓜素Ic通过抑制VCAM-1、ICAM-1、MMP-9而通过p38和JNK途径诱导E-cadherin的表达来防止细胞侵袭。因此，苦瓜素Ic可能是一个具有抗癌活性的有希望的候选化合物。
Momordin Ic was previously found to induce liver cancer cell apoptosis and autophagy. To further elucidate the anti-cancer activity of Momordin Ic, we analyzed the suppressive effects of Momordin Ic on cell migration and invasion. We also investigated the mechanisms associated with MMP-9, adhesion molecules and signaling transductions. The results demonstrated that Momordin Ic effectively prevented cell attachment, migration and invasion. E-cadherin, mediation of homotypic adhesion was induced while VCAM-1 and ICAM-1 and MMP-9 were inhibited. Momordin Ic influenced phosphorylations of p38, JNK and Erk with VEGF. p38 effectively regulated expressions of E-cadherin, VCAM-1 and ICAM-1. JNK greatly contributed to E-cadherin alteration. Erk hardly modified E-cadherin, VCAM-1, ICAM-1 and MMP-9 although Erk phosphorylation decreased by Momordin Ic. These results revealed Momordin Ic prevent cell invasion by inhibiting VCAM-1, ICAM-1, MMP-9 but inducing E-cadherin expression via p38 and JNK pathways. Thus momordin Ic may be a promising candidate with anti-cancer bioactivity.