摘要
背景:一些软体动物血蓝蛋白(Hcs)具有显着的免疫和抗肿瘤潜力,使其能够在肿瘤学中应用。与多柔比星相比,在膀胱癌永久性 T24 细胞系和正常尿路上皮细胞系 HL 10/29 体外研究了来自海洋蜗牛 Rapana venosa (RvH)、巨型锁孔帽贝 Megathura crenulata (KLH) 和花园蜗牛螺旋 ( HlH) 的 HCS 及其不同衍生物的抗肿瘤活性。 方法: 使用WST-1测定法和BrdU ELISA测定法测定所测试的Hcs的抗增殖活性。两种尿路上皮细胞系的形态变化均通过荧光显微镜证实。使用二维聚丙烯酰胺凝胶电泳(2D-PAGE)和质谱法对膀胱癌细胞系在功能单位(FU)βc-HlH-h处理前后的蛋白质组学分析揭示了一些蛋白质表达的差异。 结果: 研究证明T24肿瘤细胞系具有剂量和时间依赖性,对被测亚型的作用敏感,并且它对这些血蓝蛋白的FU糖基化。在与结构亚基(βc-HlH,RvHI和RvHII)和FU(βc-HlH-h和RvHII-e)孵育后观察到T24细胞生长的选择性抑制。此外,荧光显微照片未显示正常尿路上皮细胞系HL 10/29的凋亡或坏死改变。FU βc-HlH-h表现出最高的抗增殖作用(类似于阿霉素),其中观察到肿瘤细胞中主要是凋亡和较少的晚期凋亡或坏死变化。通过蛋白质组分析鉴定的几种下调和上调蛋白可能与细胞凋亡途径有关。 结论: 本研究阐明了Hcs对Т24癌细胞系的细胞毒性作用的选择性。这是在FU βc-HlH-h影响下T24人膀胱癌细胞中蛋白质表达的第一篇报道。这可能是由于暴露在βc-HlH-h表面上的富含甲基化己糖的特定低聚糖结构。
关键词: 血蓝蛋白,细胞毒性作用,Т24膀胱癌永久性细胞系,蛋白质组学分析,细胞凋亡,蛋白表达。
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