转基因-[Pt (胺) Cl () 2 () PPh () 3 () ]复合体在胃癌细胞中准线粒体和内分泌网膜
Jorge Melones-Herrero1,2,3, Patricia Delgado-Aliseda1,2,3, Sofía Figueiras1,2,3
1Department of Biochemistry, School of Medicine, Autonomous University of Madrid (UAM), 28029 Madrid, Spain.
新的 (II) 复合物,P1和P2,在胃癌治疗中显示出前景. P2比思丁对癌细胞更有效,对健康细胞的毒性较低,提供了潜在的新疗法.
科学领域:
- 在瘤学瘤学.
- 药用化学 医学化学
- 分子生物学分子生物学
背景情况:
- 尽管在诊断和治疗方面取得了进展,但胃癌的预后仍然很差.
- 基于的化疗是标准的,但受到毒性和疗效的限制.
- 转 (II) 复合物正在作为潜在的替代品进行研究.
研究的目的:
- 合成和评估两种新的基于素的 (II) 复合物,P1和P2.
- 评估它们在胃癌细胞中的细胞毒性和作用机制.
- 为了比较它们与西斯的疗效和毒性.
主要方法:
- 合成跨-[Pt (胺) Cl2 (胺) PPh3) ]复合体 (P1和P2).
- 对胃癌和健康细胞的细胞毒性分析.
- 检测反应性氧物种的产生,DNA损伤和线粒体膜潜力.
- 对与亡相关的蛋白质 (BAX/BAK,BIM,MCL1) 和内分泌网膜压力标志物的西部斑分析 (p62,LC3).
主要成果:
- P2对胃癌细胞表现出显著的细胞毒性,表现优于西斯.
- 与西斯普拉丁相比,P2在健康细胞中的毒性略低.
- 这两种复杂物都通过一种内在途径诱导了亡,涉及ROS生成,DNA损伤和线粒体脱极化.
- 此外,P2还诱导了细胞内网膜应激,并影响了自标志物.
结论:
- 以素为基础的 (II) 复合物,特别是P2,代表了新的胃癌疗法的有希望的候选人.
- P2的疗效和降低的毒性概况需要在临床前模型中进行进一步的研究.
- 阐明生物分子机制,包括亡和ER应激诱导,为开发这些药物提供了基础.
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