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利多卡因通过调控 miR-539/EGFR 轴抑制肺癌细胞的增殖和转移。

Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis.

机构信息

a Department of Anesthesiology, China-Japan Union Hospital of Jilin University , Changchun , China.

出版信息

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2866-2874. doi: 10.1080/21691401.2019.1636807.

DOI:10.1080/21691401.2019.1636807
PMID:31299862
Abstract

Despite the medical uses of lidocaine has been well-characterized, the study of lidocaine's pharmacological function other the anaesthetic effect was never stopped. This study designed to reveal the effect of lidocaine on the growth and metastasis of lung cancer in vitro. A549 and NCI-H1299 cells were treated by lidocaine for 24 h. miR-539 expression in cell was silenced by transfection with the specific inhibitor. The changes in cell growth and metastasis were determined using CCK-8 assay and western blot. Luciferase activity assay was performed to assay if EGFR was a target of miR-539. Western blot was used to test the activation of EGFR downstream signalling. Lidocaine suppressed the viability, migration, and invasion of A549 and NCI-H1299 cells while induced apoptotic death. Lidocaine elevated the expression of miR-539. The anti-tumour properties of lidocaine towards A549 and NCI-H1299 cells were partially attenuated when miR-539 was silenced. EGFR was a target of miR-539. Lidocaine repressed the activation of ERK and PI3K/AKT pathways also via regulating miR-539. The anti-growth and anti-metastatic effects of lidocaine towards lung cancer cells. The anti-tumour properties of lidocaine may be partial via up-regulation of miR-539, which blocked EGFR signalling by directly binding with EGFR.

摘要

尽管利多卡因的医学用途已得到充分证实,但人们从未停止过对其麻醉作用以外的药理学功能的研究。本研究旨在揭示利多卡因对体外肺癌生长和转移的影响。用利多卡因处理 A549 和 NCI-H1299 细胞 24 小时。用特异性抑制剂转染沉默细胞中 miR-539 的表达。用 CCK-8 测定法和 Western blot 测定细胞生长和转移的变化。荧光素酶活性测定法用于测定 EGFR 是否是 miR-539 的靶标。Western blot 用于测试 EGFR 下游信号通路的激活情况。利多卡因抑制 A549 和 NCI-H1299 细胞的活力、迁移和侵袭,同时诱导细胞凋亡。利多卡因上调 miR-539 的表达。当沉默 miR-539 时,利多卡因对 A549 和 NCI-H1299 细胞的抗肿瘤特性部分减弱。EGFR 是 miR-539 的靶标。利多卡因还通过调节 miR-539 抑制 ERK 和 PI3K/AKT 通路的激活。利多卡因对肺癌细胞的生长和转移具有抑制作用。利多卡因的抗肿瘤特性可能部分通过上调 miR-539 来实现,miR-539 通过直接与 EGFR 结合阻断 EGFR 信号通路。

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