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微囊藻毒素-LR 通过激活 ERK/VASP/ezrin 通路诱导 DU145 细胞微丝重排和细胞侵袭。

Microcystin-LR induced microfilament rearrangement and cell invasion by activating ERK/VASP/ezrin pathway in DU145 cells.

机构信息

School of Life Science and Technology, Weifang Medical University, Weifang, PR China.

School of Life Science and Technology, Weifang Medical University, Weifang, PR China.

出版信息

Toxicon. 2022 Apr 30;210:148-154. doi: 10.1016/j.toxicon.2022.02.023. Epub 2022 Mar 3.

Abstract

Microcystin-LR (MC-LR) is an environmental toxin that is synthesized by cyanobacteria and considered a potential human carcinogen. However, the role of MC-LR in prostate cancer progression has not been elucidated. The purpose of this study was to investigate the effect of MC-LR on prostate cancer cell invasion and its underlying mechanisms. Transwell assay was performed, and the result showed that MC-LR increased DU145 cell invasion in a concentration-dependent manner. The result of Western blot showed that MC-LR promoted ERK phosphorylation, while enhancing VASP and ezrin phosphorylation. Moreover, PD0325901 was used to verify the role of the ERK/VASP/ezrin axis in MC-LR-promoted cell invasion. The results revealed that MC-LR promoted microfilament rearrangement and cell invasion by activating the ERK/VASP/ezrin pathway in DU145 cells. Finally, in vivo assay was performed, and the result suggested that MC-LR promoted p-ERK, p-VASP and p-ezrin expression and local invasion in nude mice model. Taken together, our data proved that MC-LR induced microfilament rearrangement and cell invasion by activating the ERK/VASP/ezrin pathway in DU145 cells.

摘要

微囊藻毒素-LR(MC-LR)是一种由蓝藻合成的环境毒素,被认为是一种潜在的人类致癌物。然而,MC-LR 在前列腺癌进展中的作用尚未阐明。本研究旨在探讨 MC-LR 对前列腺癌细胞侵袭的影响及其潜在机制。通过 Transwell 实验发现,MC-LR 以浓度依赖的方式促进 DU145 细胞侵袭。Western blot 结果表明,MC-LR 促进 ERK 磷酸化,同时增强 VASP 和 ezrin 的磷酸化。此外,使用 PD0325901 验证了 ERK/VASP/ezrin 轴在 MC-LR 促进细胞侵袭中的作用。结果表明,MC-LR 通过激活 DU145 细胞中的 ERK/VASP/ezrin 通路促进微丝重排和细胞侵袭。最后,进行体内实验,结果表明 MC-LR 促进了裸鼠模型中 p-ERK、p-VASP 和 p-ezrin 的表达和局部侵袭。综上所述,我们的数据证明 MC-LR 通过激活 ERK/VASP/ezrin 通路诱导 DU145 细胞中的微丝重排和细胞侵袭。

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