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异去甲莪术二酮通过抑制p38丝裂原活化蛋白激酶/核因子κB信号通路来抑制人乳腺癌MDA-MB-231细胞的迁移和侵袭。

Isoalantolactone inhibits the migration and invasion of human breast cancer MDA-MB-231 cells via suppression of the p38 MAPK/NF-κB signaling pathway.

作者信息

Wang Jing, Cui Li, Feng Liang, Zhang Zhenhai, Song Jie, Liu Dan, Jia Xiaobin

机构信息

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.

出版信息

Oncol Rep. 2016 Sep;36(3):1269-76. doi: 10.3892/or.2016.4954. Epub 2016 Jul 20.

DOI:10.3892/or.2016.4954
PMID:27461575
Abstract

Isoalantolactone is a bioactive sesquiterpene lactone isolated from the flowering plant Inula helenium L. This study was conducted to assess the anti-migratory and anti-invasive activities of isoalantolactone in MDA-MB-231 cells, and to explore the underlying mechanisms. Wound-healing and Transwell chambers assays demonstrated that isoalantolactone inhibited the adhesion, migration and invasion of MDA-MB-231 cells. The activity and expression of MMP-2 and MMP-9 were downregulated by isoalantolactone in a dose-dependent manner. Additionally, isoalantolactone markedly decreased the p-p38 MAPK level, whereas no significant change in p-ERK1/2 and p-JNK1/2 was noted. The downregulation of MMP-2 and MMP-9 protein expression and suppression of in vitro invasion might be associated with the blockade of p38 MAPK activation. Furthermore, isoalantolactone blocked the translocation of NF-κB p65 from the cytoplasm into the nucleus. These results revealed that isoalantolactone inhibited the adhesion, migration and invasion of MDA-MB-231 cells via suppression of the p38 MAPK/NF-κB signaling pathway, and isoalantolactone might be an alternative treatment for breast cancer.

摘要

异土木香内酯是从开花植物土木香(Inula helenium L.)中分离出的一种具有生物活性的倍半萜内酯。本研究旨在评估异土木香内酯对MDA - MB - 231细胞的抗迁移和抗侵袭活性,并探讨其潜在机制。伤口愈合实验和Transwell小室实验表明,异土木香内酯可抑制MDA - MB - 231细胞的黏附、迁移和侵袭。异土木香内酯以剂量依赖的方式下调MMP - 2和MMP - 9的活性及表达。此外,异土木香内酯显著降低p - p38 MAPK水平,而p - ERK1/2和p - JNK1/2未出现明显变化。MMP - 2和MMP - 9蛋白表达的下调及体外侵袭的抑制可能与p38 MAPK激活的阻断有关。此外,异土木香内酯可阻止NF - κB p65从细胞质向细胞核的转位。这些结果表明,异土木香内酯通过抑制p38 MAPK/NF - κB信号通路抑制MDA - MB - 231细胞的黏附、迁移和侵袭,异土木香内酯可能是乳腺癌的一种替代治疗药物。

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