Department of Neurosurgery, Quzhou Hospital affiliated of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China.
Cell Transplant. 2022 Jan-Dec;31:9636897221092778. doi: 10.1177/09636897221092778.
Glioblastoma is the most frequent, as well as aggressive kind of high-grade malignant glioma. Chemoresistance is posing a significant clinical barrier to the efficacy of temozolomide-based glioblastoma treatment. By suppressing xeroderma pigmentosum group A (XPA), a pivotal DNA damage recognition protein implicated in nucleotide excision repair (NER), we devised a novel method to enhance glioblastoma therapy and alleviate temozolomide resistance. On the basis of preliminary assessment, we found that XPA dramatically increased in glioblastoma compared with normal cells and contributed to temozolomide resistance. By constructing XPA stably knockdown cells, we illustrate that XPA protects glioma cells from temozolomide-triggered reproductive cell death, apoptosis, as well as DNA repair. Besides, XPA silencing remarkably enhances temozolomide efficacy . This study revealed a crucial function of XPA-dependent NER in the resistance of glioma cells to temozolomide.
胶质母细胞瘤是最常见也是侵袭性最强的高级别恶性胶质瘤。化疗耐药性是替莫唑胺为基础的胶质母细胞瘤治疗疗效的一个重大临床障碍。通过抑制 Xeroderma pigmentosum 组 A（XPA），一种在核苷酸切除修复（NER）中起关键作用的 DNA 损伤识别蛋白，我们设计了一种新的方法来增强胶质母细胞瘤的治疗效果并减轻替莫唑胺耐药性。基于初步评估，我们发现 XPA 在胶质母细胞瘤中与正常细胞相比显著增加，并导致替莫唑胺耐药性。通过构建 XPA 稳定敲低细胞，我们表明 XPA 保护神经胶质瘤细胞免受替莫唑胺引发的生殖细胞死亡、细胞凋亡和 DNA 修复。此外，XPA 沉默显著增强了替莫唑胺的疗效。这项研究揭示了 XPA 依赖性 NER 在胶质母细胞瘤细胞对替莫唑胺耐药性中的关键作用。
