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肉桂提取物通过 FAK 到 ERK 途径减少 u-PA/MMP 表达抑制人肺癌细胞侵袭。

Cinnamomum Cassia Extracts Suppress Human Lung Cancer Cells Invasion by Reducing u-PA/MMP Expression through the FAK to ERK Pathways.

机构信息

Department of Nutrition, Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan, ROC.

Departmant of Ophthalmology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.

出版信息

Int J Med Sci. 2018 Jan 1;15(2):115-123. doi: 10.7150/ijms.22293. eCollection 2018.

Abstract

exhibits antioxidative, apoptotic, and cytostatic properties. These activities have been attributed to the modulation of several biological processes and are beneficial for possible pharmaceutical applications. However, the potential of in retarding lung adenocarcinoma cells metastasis remains ambiguous. We determined whether extract (CCE) reduces metastasis of human lung adenocarcinoma cells. The results showed that CCE treatment (up to 60 μg/mL) for 24 h exhibited no cytotoxicity on the A549 and H1299 cell lines but inhibited the motility, invasiveness, and migration of these cells by repressing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA). CCE also impaired cell adhesion to collagen. CCE significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p-extracellular signal-regulated kinases (ERK)1/2, and Ras homolog gene family (Rho)A expression. CCE showed anti-metastatic activity of A549 and H1299 cells by repressing u-PA/MMP-2 via FAK to ERK1/2 pathways. These findings may facilitate future clinical trials of lung adenocarcinoma chemotherapy to confirm the promising results.

摘要

表现出抗氧化、凋亡和细胞抑制特性。这些活性归因于对几种生物过程的调节,并且有益于可能的药物应用。然而,在延缓肺腺癌细胞转移方面的潜力仍不清楚。我们确定了 是否可以减少人类肺腺癌细胞的转移。结果表明,CCE 处理(高达 60μg/mL)24 小时对 A549 和 H1299 细胞系没有细胞毒性,但通过抑制基质金属蛋白酶(MMP)-2 和尿激酶型纤溶酶原激活剂(u-PA)来抑制这些细胞的运动性、侵袭性和迁移。CCE 还损害了细胞对胶原蛋白的黏附性。CCE 显著降低了 p-黏着斑激酶(FAK)Tyr397、p-FAK Tyr925、p-细胞外信号调节激酶(ERK)1/2 和 Ras 同源基因家族(Rho)A 的表达。CCE 通过 FAK 抑制 u-PA/MMP-2 来抑制 ERK1/2 通路,从而表现出对 A549 和 H1299 细胞的抗转移活性。这些发现可能有助于未来的肺腺癌化疗临床试验来确认有希望的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/5765724/4b312097a975/ijmsv15p0115g001.jpg

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