School of Life Science and Technology, Weifang Medical University, Weifang, PR China.
School of Life Science and Technology, Weifang Medical University, Weifang, PR China.
Toxicon. 2022 Apr 30;210:148-154. doi: 10.1016/j.toxicon.2022.02.023. Epub 2022 Mar 3.
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.
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。
