Bratisl Lek Listy. 2022;123(10):752-757. doi: 10.4149/BLL_2022_121.
Increased ROS has been reported to cause a change in E- and N-cadherin levels, and consequently promotes migrative behaviors in pancreas and breast cancer cells. In this study, the effect of a sublethal dose of H2O2 on E- and N-cadherin levels, and on migrative behaviors of PCa cells was investigated.
To determine a sublethal concentration of H2O2 on cell proliferation and ROS production were examined using WST-1 and DCFH-DA assays, respectively. E- and N-cadherin protein and mRNA levels were investigated by western blotting and real-time PCR, respectively. The migrative potentials of the cells were examined by Cytoselect 96-well cell migration assay.
Treatment of the PCa cells with a sublethal dose of H2O2 results in a decrease in E-cadherin and an increase in N-cadherin levels, at both mRNA and protein levels. However, inhibition of ERK using PD98059 abolishes the effects of H2O2. In addition, the cells that were treated with H2O2 have gained further migrative abilities compared to control cells, and this ability was repressed when PD98059 was used together with H2O2.
Increased ROS alters E- and N-cadherin levels in an ERK-dependent manner and thereby promotes the migrative abilities of PCa cells (Fig. 3, Ref. 32).
已有报道称活性氧(ROS)的增加会导致 E-和 N-钙粘蛋白水平发生变化,从而促进胰腺和乳腺癌细胞的迁移行为。在本研究中,研究了亚致死剂量的 H2O2 对 E-和 N-钙粘蛋白水平以及前列腺癌细胞迁移行为的影响。
分别使用 WST-1 和 DCFH-DA 测定来确定 H2O2 对细胞增殖和 ROS 产生的亚致死浓度。通过 Western blot 和实时 PCR 分别研究 E-和 N-钙粘蛋白蛋白和 mRNA 水平。通过 Cytoselect 96 孔细胞迁移测定来检测细胞的迁移潜力。
用亚致死剂量的 H2O2 处理前列腺癌细胞会导致 E-钙粘蛋白水平降低,E-和 N-钙粘蛋白的 mRNA 和蛋白水平均升高。然而,使用 PD98059 抑制 ERK 会消除 H2O2 的作用。此外,与对照细胞相比,用 H2O2 处理的细胞获得了进一步的迁移能力,而当 PD98059 与 H2O2 一起使用时,这种能力受到抑制。
ROS 的增加以 ERK 依赖性方式改变 E-和 N-钙粘蛋白水平,从而促进前列腺癌细胞的迁移能力(图 3,参考文献 32)。