开发一种能够逆转多重药物耐药性瘤组合化疗的aptamer
Xiaohong Wen1,2,3, Zhixiang Huang1,3,4, Xiaohai Yang1,2,3
1State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, China.
概括
一种新开发的DNA吸收剂有效地逆转了肝癌细胞中的多药性耐药性. 这种胺体通过增加药物积累来增强化疗效,显示出改善癌症治疗的巨大潜力.
科学领域:
- 生物技术是生物技术.
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 多药耐药性 (MDR) 显著限制化疗在治疗各种癌症中的有效性.
- 开发可逆转MDR的药物对于提高治疗结果和克服治疗失败至关重要.
研究的目的:
- 选和表征一种能够在人类肝细胞癌 (HCC) 细胞中逆转MDR的DNA吸收体.
- 评估所选的阿普塔默作为治疗肝癌治疗的治疗剂的潜力.
主要方法:
- 通过指数式丰富 (SELEX) 进行基于细胞的连接体系统演化,用于识别对抗多克索鲁比 (DOX) 耐药的HepG2/DOX细胞的阿帕特马.
- 研究了aptamer的亲和力,特异性和MDR逆转的机制.
- 使用异种移植小鼠模型进行了体内研究,以评估治疗疗效.
主要成果:
- 鉴定出一种特定的DNA胺体,d3,对HepG2/DOX细胞具有很高的亲和力和特异性,向多药耐药性蛋白1 (MDR1).
- 阿普塔默d3证明了其阻断MDR的能力,增加化疗剂 (DOX,温克里斯,帕克利塔塞尔) 的细胞内积累,并增强癌细胞杀死.
- 在体内,阿帕特马尔d3和DOX的联合治疗显著抑制了瘤的生长.
结论:
- 这种DNA的aptamerd3显示出作为一种治疗剂的显著潜力,可以逆转瘤MDR.
- 结合aptamer d3与常规化疗药物,为改善肝癌治疗结果提供了一个有前途的策略.
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