Liu Ziwei, Liu Zhimei, Zhang Xiulan, Xue Pingping, Zhang Heng
School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Xiongchu Avenue, Wuhan, China.
Humanwell Healthcare (group) Co. Ltd, Gaoxing Avenue, Wuhan, China.
Biomed Pharmacother. 2014 May;68(4):439-45. doi: 10.1016/j.biopha.2014.03.003. Epub 2014 Mar 20.
In the article, we investigated the anti-metastasis mechanism of RY10-4, an anti-tumor compound derived from protoapigenone, in breast tumor cells MB-MDA-231. The analog of protoapigenone with an unaromatic B-ring was verified to suppress the proliferation of several tumor cells by previous research that also showed that several tumor progression such as inducing apoptosis and anti-angiogenesis could be acted on by RY10-4. In the article, we investigated the mechanism about how RY10-4 suppressed the invasion of MDA-MB-231. Firstly, the transwells assays with and without matrigel were adapted to evaluate the anti-metastasis and anti-invasion activity. Much research had demonstrated that the ECM and E-cadherin/β-catenin complex play an important role in cell adhesion and the formation of the cell skeleton, and as we knew the abnormal and absent expression of ECM and E-cadherin/β-catenin complex are found in many malignant cells. The result demonstrated that the amount and distribution of E-cadherin/β-catenin complex were backed on track by RY10-4, and the expression of MMP-2/9 in MDA-MB-231, which functions as a major negative factor of ECM, was down-regulated after co-cultured with RY10-4. Furthermore the pathway related to MMP-2/9 and E-cadherin was assessed by the western blot. As the results showed, the MAPK pathway and the spread of β-catenin were affected by RY10-4 to exert the anti-metastasis on MDA-MB-231. Collectively, the research revealed a novel anti-tumor ability of RY10-4 by inhibiting migration and invasion in MDA-MB-231.
在本文中，我们研究了源自原芹菜素的抗肿瘤化合物RY10-4在乳腺肿瘤细胞MB-MDA-231中的抗转移机制。先前的研究证实，具有非芳香性B环的原芹菜素类似物可抑制多种肿瘤细胞的增殖，该研究还表明，RY10-4可作用于多种肿瘤进展过程，如诱导凋亡和抗血管生成。在本文中，我们研究了RY10-4抑制MDA-MB-231侵袭的机制。首先，采用有无基质胶的Transwell实验评估其抗转移和抗侵袭活性。许多研究表明，细胞外基质（ECM）和E-钙黏蛋白/β-连环蛋白复合物在细胞黏附和细胞骨架形成中起重要作用，并且我们知道在许多恶性细胞中都发现了ECM和E-钙黏蛋白/β-连环蛋白复合物的异常表达或缺失。结果表明，RY10-4使E-钙黏蛋白/β-连环蛋白复合物的数量和分布恢复正常，与RY10-4共培养后，MDA-MB-231中作为ECM主要负性因子的基质金属蛋白酶-2/9（MMP-2/9）的表达下调。此外，通过蛋白质印迹法评估了与MMP-2/9和E-钙黏蛋白相关的信号通路。结果显示，RY10-4影响丝裂原活化蛋白激酶（MAPK）信号通路和β-连环蛋白的转位，从而对MDA-MB-231发挥抗转移作用。总的来说，该研究揭示了RY10-4通过抑制MDA-MB-231的迁移和侵袭而具有的一种新的抗肿瘤能力。
