利多卡因通过上调 miR-145 抑制胃癌细胞的生长、迁移和侵袭。
Lidocaine inhibits growth, migration and invasion of gastric carcinoma cells by up-regulation of miR-145.
机构信息
Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
出版信息
BMC Cancer. 2019 Mar 15;19(1):233. doi: 10.1186/s12885-019-5431-9.
BACKGROUND
Gastric cancer receives considerable attention not only because it is the most common cancer all through the world, but also because it's on the top third leading reason for cancer-related death. Lidocaine is a well-documented local anesthetic that has been reported to suppress cancer development. The study explored the effects of lidocaine on the growth, migration and invasion of the gastric carcinoma cell line MKN45 and the mechanism behind.
METHODS
The effect of lidocaine on viability, proliferation and apoptosis of MKN45 cells were analyzed by Cell Counting Kit-8 assay, BrdU staining assay and flow cytometry, respectively. Moreover, cell migration and invasion were both examined by Transwell assay. The expression of apoptosis-, migration-, and invasion-related proteins were detected by western blot. The relative expression of miR-145 was determined by qRT-PCR. Moreover, the impact which lidocaine brought on MEK/ERK and NF-κB pathways were examined by western blot.
RESULTS
Lidocaine inhibited viability, proliferation, migration, and invasion of MKN45 cells, while enhanced apoptosis. Moreover, miR-145 expression was enhanced by lidocaine; and transfection with miR-145 inhibitor increased cell viability, proliferation, migration, and invasion, but inhibited apoptosis. The up-regulation of miR-145 was partly contributed to the inhibitory effect of lidocaine on gastric cancer cell line MKN45. Finally, lidocaine inactivated MEK/ERK and NF-κB pathways via up-regulation of miR-145.
CONCLUSIONS
Our results suggested that lidocaine decreased growth, migration and invasion of MKN45 cells via regulating miR-145 expression and further inactivation of MEK/ERK and NF-κB signaling pathways.
背景
胃癌不仅因其是全球最常见的癌症而备受关注，还因其是癌症相关死亡的第三大主要原因。利多卡因是一种有充分文献记录的局部麻醉剂，据报道它具有抑制癌症发展的作用。本研究旨在探讨利多卡因对胃癌细胞系 MKN45 生长、迁移和侵袭的影响及其机制。
方法
通过细胞计数试剂盒-8 检测、BrdU 染色检测和流式细胞术分别分析利多卡因对 MKN45 细胞活力、增殖和凋亡的影响。此外，通过 Transwell 检测法检测细胞迁移和侵袭。通过 Western blot 检测凋亡、迁移和侵袭相关蛋白的表达。通过 qRT-PCR 检测 miR-145 的相对表达。此外，通过 Western blot 检测利多卡因对 MEK/ERK 和 NF-κB 通路的影响。
结果
利多卡因抑制了 MKN45 细胞的活力、增殖、迁移和侵袭，同时促进了细胞凋亡。此外，利多卡因增强了 miR-145 的表达；转染 miR-145 抑制剂增加了细胞活力、增殖、迁移和侵袭，但抑制了细胞凋亡。miR-145 的上调部分归因于利多卡因对胃癌细胞系 MKN45 的抑制作用。最后，利多卡因通过上调 miR-145 使 MEK/ERK 和 NF-κB 通路失活。
结论
我们的研究结果表明，利多卡因通过调节 miR-145 表达，进一步抑制 MEK/ERK 和 NF-κB 信号通路，降低了 MKN45 细胞的生长、迁移和侵袭。
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