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丹酚酸 A 通过 PI3K/Akt/mTOR 信号通路抑制人非小细胞肺癌血管生成拟态的形成。

Salvianolic acid A blocks vasculogenic mimicry formation in human non-small cell lung cancer via PI3K/Akt/mTOR signalling.

机构信息

Department of Thoracic Surgery, Xiang'an Hospital of Xiamen University, Xiamen, China.

Department of Thoracic Surgery, First People's Hospital of Yunnan Province, Kunming, China.

出版信息

Clin Exp Pharmacol Physiol. 2021 Apr;48(4):508-514. doi: 10.1111/1440-1681.13464. Epub 2021 Feb 2.

Abstract

Vasculogenic mimicry (VM) is associated with aggressive cancer cells. Salvianolic acid A (Sal-A), an antioxidant and anti-inflammatory agent, has bioactive properties from Salvia miltiorrhiza Bunge. Current investigation aspired to explore the activity of Sal-A in the VM formation of non-small cell lung cancer (NSCLC) and the mechanism underling this function. The CCK8, the scratch and boyden chemotaxis assay were presented to describe NSCLC cells viability, migration and invasion capabilities, respectively. The protein expression was verified by western blotting. In this report, Sal-A caused a reduction in viability, metastasis and capillaries structure formation of NSCLC cells. Additionally, Sal-A markedly prevented the key VM related proteins, containing EphA2, VE-cadherin and MMP2. Besides, Sal-A significantly diminished p-PI3K, p-Akt and p-mTOR level in NSCLC cells. More importantly, SC79 pretreatment reversed Sal-A inhibits NSCLC cells viability, metastasis and VM formation. These data exhibit that Sal-A could block VM network formation in NSCLC cells through modulating the PI3K/Akt/mTOR signalling pathway.

摘要

血管生成拟态(VM)与侵袭性癌细胞相关。丹酚酸 A(Sal-A)是一种抗氧化和抗炎剂,具有丹参中的生物活性。本研究旨在探讨 Sal-A 对非小细胞肺癌(NSCLC)VM 形成的作用及其机制。CCK8、划痕和 Boyden 趋化实验分别描述了 NSCLC 细胞的活力、迁移和侵袭能力。蛋白质表达通过 Western blot 验证。在本报告中,Sal-A 导致 NSCLC 细胞活力、转移和毛细血管结构形成减少。此外,Sal-A 显著阻止了 EphA2、VE-cadherin 和 MMP2 等关键的 VM 相关蛋白。此外,Sal-A 显著降低了 NSCLC 细胞中 p-PI3K、p-Akt 和 p-mTOR 的水平。更重要的是,SC79 预处理逆转了 Sal-A 抑制 NSCLC 细胞活力、转移和 VM 形成的作用。这些数据表明,Sal-A 可能通过调节 PI3K/Akt/mTOR 信号通路来阻断 NSCLC 细胞中的 VM 网络形成。

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