Effects and mechanism of ensartinib (X-396) on the adhesion and metastasis of non-small cell lung cancer cells.

Bin Zhang, T. Qiao, Caixia Gao
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Abstract

The current study aimed to investigate the inhibitory effect and mechanism of ensartinib on adhesion, invasion and migration of non-small cell lung cancer (NSCLC) cells, including H460 and A549. Cell adhesion test, scratch test and Transwell cell invasion test were used to detect cell adhesion, migration and invasion. RT-PCR was used to detect the expression of MMP-2 and MMP-9 in H460 and A549 cells. Western blot was used to detect the expression of MMP-2 and MMP-9 proteins, ERK signaling pathway related proteins and p-Akt. Our data showed that ensartinib inhibited adhesion, invasion and migration of H460 and A549 cells in a concentration-dependent manner (P < 0.05). Ensartinib decreased the expression of MMP-2 and MMP-9 in H460 and A549 cells (P < 0.01). It also downregulated the expression of MMP-2 and MMP-9 in H460 and A549 cells, and inhibited the expression of Ras, p-c-Raf, p-ERK 1/2 and p-Akt upstream in a concentration- and time-dependent manner. Ensartinib inhibits the adhesion, invasion and migration of NSCLC cells, and such effect is related to downregulation of MMP-2 and MMP-9 expression, inhibition of ERK signaling pathway and p-Akt expression.
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恩沙替尼(X-396)对非小细胞肺癌细胞粘附和转移的影响及机制
本研究旨在探讨恩沙替尼对非小细胞肺癌(non-small cell lung cancer, NSCLC)细胞H460和A549粘附、侵袭和迁移的抑制作用及其机制。采用细胞粘附试验、划痕试验和Transwell细胞侵袭试验检测细胞粘附、迁移和侵袭。RT-PCR检测H460和A549细胞中MMP-2和MMP-9的表达。Western blot检测MMP-2、MMP-9蛋白、ERK信号通路相关蛋白、p-Akt的表达。我们的数据显示恩沙替尼抑制H460和A549细胞的粘附、侵袭和迁移呈浓度依赖性(P < 0.05)。恩沙替尼降低了H460和A549细胞中MMP-2和MMP-9的表达(P < 0.01)。下调H460和A549细胞中MMP-2和MMP-9的表达,抑制上游Ras、p-c-Raf、p-ERK 1/2和p-Akt的表达,并呈浓度依赖性和时间依赖性。恩沙替尼抑制NSCLC细胞的粘附、侵袭和迁移,其作用机制与下调MMP-2和MMP-9的表达、抑制ERK信号通路和p-Akt的表达有关。
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