铂(iv)复合物及其配体抑制结直肠癌细胞运动,促进卷曲-7受体的表达

D. Šeklić, Milena M. Jovanović, Nevena Milivojević, M. Zivanovic
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引用次数: 0

摘要

抑制细胞运动是未来几代化疗药物有效性的必要条件。卷曲7受体(frzzled 7 receptor, FZD7)作为Wnt/β-catenin信号级联的首个蛋白,在调控细胞分化、增殖、迁移等方面发挥着重要作用。本研究旨在探讨铂(IV)复合物:[PtCl4 (dbus - s, S-eddp)] - C1及其对应的配体- L1对两种人结直肠癌细胞系(HCT-116, SW-480)治疗后细胞运动的潜在影响,以及FZD7的表达和定位。采用伤口愈合法检测细胞迁移,免疫荧光法检测FZD7蛋白表达。化合物,尤其是L1,降低了两种被测细胞系的细胞活力。它们对HCT-116细胞的作用特别好,增加了抗迁移标志物FZD7的蛋白表达,FZD7在HCT-116细胞的细胞膜上有定位。与HCT-116相比,SW-480细胞经处理后对细胞运动的抑制明显降低,FZD7受体的表达及其在细胞质中的定位明显降低。我们的研究结果表明,在检测的处理中,配体对HCT-116细胞运动的抑制效果更为显著,很可能是通过刺激分化来实现的,这可以通过促进FZD7的表达来证明。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PLATINUM(IV) COMPLEX AND ITS CORRESPONDING LIGAND SUPPRESS CELL MOTILITY AND PROMOTE EXPRESSION OF FRIZZLED-7 RECEPTOR IN COLORECTAL CANCER CELLS
Suppression of cell movement is an imperative in the effectiveness of future generations of chemotherapeutics. Frizzled 7 receptor (FZD7), as the first protein of Wnt/β-catenin signaling cascade, plays a significant role in regulation of cell differentiation, proliferation, and cell migration. This study aimed to investigate the potential effects of platinum (IV) complex: [PtCl4 (dbu-S, S-eddp)] – C1, and its corresponding ligand – L1 on cell movement, as well as the FZD7 expression and localization after treatments on two human colorectal carcinoma cell lines (HCT-116, SW-480). A Wound healing assay was used to examine cell migration, while FZD7 protein expression was examined by immunofluorescence. Chemical compounds, especially L1, reduced cell motility of both tested cell lines. They showed a particularly good effect on HCT-116 cells, increasing protein expression of the antimigratory marker FZD7 whose localization was observed on the cell membrane of HCT-116 cells. Suppression of cell movement was significantly lower in SW-480 cells after treatments, when compared to HCT-116, with an obvious decrease of FZD7 receptor expression and its localization in the cytoplasm of these cells. Our results indicate that among the examined treatments, the ligand showed more significant results in the suppression of HCT-116 cell movement, most likely through the stimulation of differentiation, which is indicated by the promotion of FZD7 expression.
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