Department of Obstetrics and Gynecology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
Department of Obstetrics and Gynecology, Zhuxi Maternal and Child Health Hospital, Shiyan 442000, Hubei Province, China.
Biosci Rep. 2018 Nov 30;38(6). doi: 10.1042/BSR20180738. Print 2018 Dec 21.
Casticin is one of the major active components isolated from Increasing studies have revealed that casticin has potential anticancer activity in various cancer cells, but its effects on breast cancer cell migration and invasion are still not well known. Therefore, the ability of cell migration and invasion in the breast cancer MDA-MB-231 and 4T1 cells treated by casticin was investigated. The results indicated that casticin significantly inhibited cell migration and invasion in the cells exposed to 0.25 and 0.50 µM of casticin for 24 h. Casticin treatment reduced matrix metalloproteinase (MMP) 9 (MMP-9) activity and down-regulated mRNA and protein expression, but not MMP-2. Casticin treatment suppressed the nuclear translocation of transcription factors c-Jun and c-Fos, but not nuclear factor-κB (NF-κB), and decreased the phosphorylated level of Akt (p-Akt). Additionally, the transfection of Akt overexpression vector to MDA-MB-231 and 4T1 cells could up-regulate MMP-9 expression concomitantly with a marked increase in cell invasion, but casticin treatment reduced Akt, p-Akt, and MMP-9 protein levels and inhibited the ability of cell invasion in breast cancer cells. Additionally, casticin attenuated lung metastasis of mouse 4T1 breast cancer cells in the mice and down-regulated MMP-9 expression in the lung tissues of mice treated by casticin. These findings suggest that MMP-9 expression suppression by casticin may act through inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which in turn results in the inhibitory effects of casticin on cell migration and invasion in breast cancer cells. Therefore, casticin may have potential for use in the treatment of breast cancer invasion and metastasis.
金雀异黄素是从 中分离得到的主要活性成分之一。越来越多的研究表明，金雀异黄素在各种癌细胞中具有潜在的抗癌活性，但它对乳腺癌细胞迁移和侵袭的影响尚不清楚。因此，研究了金雀异黄素处理的乳腺癌 MDA-MB-231 和 4T1 细胞中细胞迁移和侵袭的能力。结果表明，金雀异黄素在暴露于 0.25 和 0.50 µM 金雀异黄素 24 h 的细胞中显著抑制细胞迁移和侵袭。金雀异黄素处理降低了基质金属蛋白酶（MMP）9（MMP-9）的活性，并下调了 mRNA 和蛋白表达，但不影响 MMP-2。金雀异黄素处理抑制了转录因子 c-Jun 和 c-Fos 的核转位，但不影响核因子-κB（NF-κB），并降低了 Akt 的磷酸化水平（p-Akt）。此外，MDA-MB-231 和 4T1 细胞中 Akt 过表达载体的转染可同时上调 MMP-9 表达，并显著增加细胞侵袭，但金雀异黄素处理降低了 Akt、p-Akt 和 MMP-9 蛋白水平，并抑制了乳腺癌细胞的侵袭能力。此外，金雀异黄素在小鼠中减弱了 4T1 乳腺癌细胞的肺转移，并下调了金雀异黄素处理的小鼠肺组织中的 MMP-9 表达。这些发现表明，金雀异黄素通过抑制磷脂酰肌醇 3-激酶（PI3K）/Akt 信号通路抑制 MMP-9 表达，从而导致金雀异黄素对乳腺癌细胞迁移和侵袭的抑制作用。因此，金雀异黄素可能具有用于治疗乳腺癌侵袭和转移的潜力。
