Nitidine chloride inhibits ovarian cancer cell migration and invasion by suppressing MMP-2/9 production via the ERK signaling pathway

氯化两面针碱通过 ERK 信号通路抑制 MMP-2/9 的产生,抑制卵巢癌细胞迁移和侵袭

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作者:Xiangxiu Sun, Lin Lin, Ying Chen, Tianfeng Liu, Ronghua Liu, Zhongde Wang, Kai Mou, Jia Xu, Bo Li, Haibo Song

Abstract

Nitidine chloride (NC) has been demonstrated to exert anti-tumor effects on various types of tumor. However, no studies have investigated the anti‑metastatic effect of NC on ovarian cancer cells, and the underlying mechanisms have not yet been clearly established. The present study aimed to determine the effect of NC on the migration and invasion of ovarian cancer cells. Cell viability and proliferation of ovarian cancer cells were assessed by MTT assay. A scratch wound healing assay and Transwell assays were performed to detect migration and invasion of cells, respectively. The expression levels of matrix metalloproteinase (MMP)‑2 and 9 were detected at the mRNA and protein level following stimulation with NC. Subsequently, the expression of mitogen‑activated protein kinases was detected by western blot analysis. Finally, an inhibitor of extracellular signal‑regulated kinase (ERK) was applied to investigate the effect of NC on the expression of MMP‑2/9 as well as the migration and invasion of cells. It was found that NC suppressed the proliferation, migration and invasion of A2780 ovarian cancer cells. NC downregulated MMP‑2 and MMP‑9 in a dose‑ and time‑dependent manner. In addition, NC was also able to downregulate phosphorylation of ERK. Furthermore, by applying an ERK inhibitor, U0126, the effect of NC on the expression of MMP-2/9 and inhibition of cell migration and invasion was verified. Taken together, these results demonstrated that NC inhibited the migration and invasion of ovarian cancer cells via the ERK signaling pathway.

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