Sun Xiangxiu, Lin Lin, Chen Ying, Liu Tianfeng, Liu Ronghua, Wang Zhongde, Mou Kai, Xu Jia, Li Bo, Song Haibo
Department of Gynecology and Obsterics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
Prenatal Diagnosis Center, Zibo Maternal and Child Health Hospital, Zibo, Shandong 255000, P.R. China.
Mol Med Rep. 2016 Apr;13(4):3161-8. doi: 10.3892/mmr.2016.4929. Epub 2016 Feb 23.
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.
氯化两面针碱（NC）已被证明对多种类型的肿瘤具有抗肿瘤作用。然而，尚无研究调查NC对卵巢癌细胞的抗转移作用，其潜在机制也尚未明确确立。本研究旨在确定NC对卵巢癌细胞迁移和侵袭的影响。通过MTT法评估卵巢癌细胞的细胞活力和增殖。分别进行划痕伤口愈合试验和Transwell试验以检测细胞的迁移和侵袭。在用NC刺激后，在mRNA和蛋白质水平检测基质金属蛋白酶（MMP）-2和9的表达水平。随后，通过蛋白质印迹分析检测丝裂原活化蛋白激酶的表达。最后，应用细胞外信号调节激酶（ERK）抑制剂来研究NC对MMP-2/9表达以及细胞迁移和侵袭的影响。结果发现，NC抑制了A2780卵巢癌细胞的增殖、迁移和侵袭。NC以剂量和时间依赖性方式下调MMP-2和MMP-9。此外，NC还能够下调ERK的磷酸化。此外，通过应用ERK抑制剂U0126，验证了NC对MMP-2/9表达的影响以及对细胞迁移和侵袭的抑制作用。综上所述，这些结果表明NC通过ERK信号通路抑制卵巢癌细胞的迁移和侵袭。
