Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan.
Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Cancer Med. 2018 Aug;7(8):3945-3954. doi: 10.1002/cam4.1635. Epub 2018 Jun 28.
The incidence and mortality rate of urological cancers is increasing yearly. Niclosamide has been repurposed as an anti-cancer drug in recent years. Synthesized derivative of niclosamide was testified for its anti-cancer activity in urological cancers. MTT assay was used to measure the cytotoxicity effect of niclosamide and its derivatives in urological cancer cell lines. Migratory ability was monitored by scratch migration assay. Apoptosis and cell cycle changes were analyzed by annexin V and PI staining. The apoptosis-related signal proteins were evaluated by western blotting. T24 had the best drug sensitivity with the lowest IC in niclosamide and B17 treatment than DU145 and Caki-1 cells. After niclosamide and B17 treatment, the mitotic cells were decreased, but apoptotic bodies and morphology changes were not prominent in T24, Caki-1, and DU145 cells. The migratory ability was inhibited in niclosamide treatment than control group on Caki-1 cells and niclosamide and B17 treatment than control group on DU145 cells. Early apoptosis cells were increased after niclosamide and B17 treatment than control group without cell cycle changes in T24, Caki-1, and DU145 cells. Programmed cell death was activated majorly through PAPR and bcl-2 in T24 and caspase-3 in Caki-1 cells, respectively. Niclosamide and B17 derivative had good ability in inhibition proliferation and migratory ability in T24, Caki-1, and DU145 cells without prominent morphology and apoptotic body changes. UCC cells are more sensitive to niclosamide and B17 treatment. Early apoptosis was induced after niclosamide and B17 treatment through different mechanisms in T24, Caki-1, and DU145 cells.
泌尿系统癌症的发病率和死亡率逐年上升。近年来，氯硝柳胺已被重新用作抗癌药物。氯硝柳胺的合成衍生物已被证明在泌尿系统癌症中具有抗癌活性。MTT 法用于测量氯硝柳胺及其衍生物在泌尿系统癌细胞系中的细胞毒性作用。划痕迁移实验监测迁移能力。通过 Annexin V 和 PI 染色分析细胞凋亡和细胞周期变化。通过 Western blot 评估凋亡相关信号蛋白。T24 对氯硝柳胺和 B17 的药物敏感性最好，IC 低于 DU145 和 Caki-1 细胞。在氯硝柳胺和 B17 处理后，有丝分裂细胞减少，但 T24、Caki-1 和 DU145 细胞中凋亡小体和形态变化不明显。与对照组相比，氯硝柳胺处理可抑制 Caki-1 细胞的迁移能力，而氯硝柳胺和 B17 处理可抑制 DU145 细胞的迁移能力。与对照组相比，氯硝柳胺和 B17 处理后 T24、Caki-1 和 DU145 细胞中的早期凋亡细胞增加，但细胞周期无变化。T24 中主要通过 PAPR 和 bcl-2 激活程序性细胞死亡，而 Caki-1 细胞中则通过 caspase-3 激活。氯硝柳胺和 B17 衍生物在 T24、Caki-1 和 DU145 细胞中具有良好的抑制增殖和迁移能力，而形态和凋亡小体变化不明显。UCC 细胞对氯硝柳胺和 B17 处理更为敏感。氯硝柳胺和 B17 处理后通过不同机制在 T24、Caki-1 和 DU145 细胞中诱导早期凋亡。
