天然小分子逆向Xeroderma Pigmentosum补充组C (XPC) 在细胞癌中缺陷介导的耐药性
Ruihong Chen1, Hang Hong Lo2, Chenxu Yang2
1Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China; Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China; Institute of Laboratory Medicine, School of Medical Technology, Guangdong Medical University, Dongguan, China.
XPC基因缺陷有助于癌的耐药性. 发现六种天然化合物通过上调XPC基因来逆转这种耐药性,从而提供了潜在的新疗法.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 癌对放射治疗和化疗等常规疗法表现出耐药性.
- XPC基因在癌耐药性中的作用以前是未知的,尽管它与其他癌症的耐药性有关.
- 自然小分子越来越多地用于组合疗法,以提高药物敏感性和减少癌症治疗中的副作用.
研究的目的:
- 调查XPC基因缺陷与癌中药物耐药性之间的相关性.
- 通过上调XPC表达来识别能够逆转癌药物耐药性的天然小分子.
主要方法:
- 免疫组织化学 (IHC) 和TCGA数据库分析,以评估瘤中的XPC表达及其与临床数据的相关性.
- 建立XPC-knockdown (XPC-KD) 癌细胞模型,以选来自134种天然化合物的XPC基因增强剂.
- 使用MTT细胞毒性测定与FDA批准的药物结合使用识别的增强剂的验证.
- 机理学研究包括基因分析,ROS检测和细胞成像,以阐明药物耐药性途径.
主要成果:
- 与相邻组织相比,癌组织中的XPC基因表达显着较低,特别是在转移的晚期 (第四阶段) 组织中.
- 六种天然的小分子 (tectorigenin,pinostilbene,d-pinitol,polygalasaponin F,atractylenolide III和astragaloside II) 被确定为XPC表达的强有力的增强剂.
- 使用这些天然化合物和FDA批准的药物的联合治疗表明XPC-KD癌细胞的敏感性增加.
- 鉴定出GSTP1/ROS轴是药物耐药XPC-KD癌细胞中激活的关键机制.
结论:
- XPC基因缺陷与癌中药物耐药性有关,由GSTP1/ROS轴介导.
- 这六种已识别的天然小分子通过提高XPC表达的调节来有效地逆转耐药性.
- 这些天然化合物有望作为辅助疗法来克服癌中抗药性.
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