载药纳米粒喜树碱：结肠癌细胞中 DNA 修复机制的表观遗传调控。

Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells.

机构信息

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Aljouf Province, Saudi Arabia.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan 43400, Selangor, Malaysia.

出版信息

Molecules. 2021 Sep 6;26(17):5414. doi: 10.3390/molecules26175414.

DOI:10.3390/molecules26175414

PMID:34500845

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8434408/

Abstract

Molecular crosstalk between the cellular epigenome and genome converge as a synergistic driver of oncogenic transformations. Besides other pathways, epigenetic regulatory circuits exert their effect towards cancer progression through the induction of DNA repair deficiencies. We explored this mechanism using a camptothecin encapsulated in β-cyclodextrin-EDTA-FeO nanoparticles (CPT-CEF)-treated HT29 cells model. We previously demonstrated that CPT-CEF treatment of HT29 cells effectively induces apoptosis and cell cycle arrest, stalling cancer progression. A comparative transcriptome analysis of CPT-CEF-treated versus untreated HT29 cells indicated that genes controlling mismatch repair, base excision repair, and homologues recombination were downregulated in these cancer cells. Our study demonstrated that treatment with CPT-CEF alleviated this repression. We observed that CPT-CEF exerts its effect by possibly affecting the DNA repair mechanism through epigenetic modulation involving genes of , , and . Hence, we propose that CPT-CEF could be a DNA repair modulator that harnesses the cell's epigenomic plasticity to amend DNA repair deficiencies in cancer cells.

摘要

细胞表观基因组和基因组之间的分子串扰作为致癌转化的协同驱动因素汇聚在一起。除了其他途径外，表观遗传调控回路还通过诱导 DNA 修复缺陷来发挥其对癌症进展的作用。我们使用喜树碱包封在β-环糊精-EDTA-FeO 纳米粒子（CPT-CEF）处理的 HT29 细胞模型探索了这种机制。我们之前证明 CPT-CEF 处理 HT29 细胞可有效诱导细胞凋亡和细胞周期停滞，从而阻止癌症进展。CPT-CEF 处理的 HT29 细胞与未处理的 HT29 细胞的比较转录组分析表明，控制错配修复、碱基切除修复和同源重组的基因在这些癌细胞中下调。我们的研究表明，CPT-CEF 治疗缓解了这种抑制。我们观察到 CPT-CEF 通过可能影响涉及、、和的基因的表观遗传调节来发挥其作用，从而影响 DNA 修复机制。因此，我们提出 CPT-CEF 可能是一种 DNA 修复调节剂，它利用细胞的表观基因组可塑性来纠正癌细胞中的 DNA 修复缺陷。