Goswami Sakshi, Verma Yeshvandra, Rana S V S
Department of Toxicology, Ch. Charan Singh University, Meerut, 250004, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 26. doi: 10.1007/s00210-025-04355-w.
Temozolomide (TMZ) is one of the alkylating drugs that are preferably employed to treat human glioblastoma (GBM). However, its immune escape and resistance by GBM limit the survival of patients. The present in vitro study was undertaken to investigate whether AgNPs or TiONPs can enhance the sensitivity of GBM to TMZ through apoptotic and/or inflammatory responses. Human glioblastoma U87MG cells were exposed to different concentrations of TMZ, AgNPs, and TiONPs after determining respective IC values for 24 h at 37 °C under a 5% CO atmosphere. Thereafter, biomarkers of LPO (malondialdehyde), apoptosis (caspase 3, 9), inflammation (TNF-α and IL-12), and DNA fragmentation (CAD) were assayed. Acridine orange/ethidium bromide staining of GBM was also performed. Combined treatments of GBM with TMZ and AgNPs or TiONPs showed a mild stimulatory effect on selected biomarkers of LPO (MDA), apoptosis (caspase3, 9), DNA fragmentation (CAD), and inflammatory cytokines (TNF-α and IL-12) in comparison to those GBM cells treated with TMZ alone. Microscopical results on apoptosis supported these results. It is suggested that overexpression of drug efflux transporters, increased apoptosis, inflammation, and drug delivery directly to cells might have contributed to enhanced protective effects of TMZ, in combination with nanoparticles.
替莫唑胺（TMZ）是一种优选用于治疗人类胶质母细胞瘤（GBM）的烷化剂药物。然而，GBM的免疫逃逸和耐药性限制了患者的生存期。本体外研究旨在探讨银纳米颗粒（AgNPs）或二氧化钛纳米颗粒（TiONPs）是否能通过凋亡和/或炎症反应增强GBM对TMZ的敏感性。在37℃、5%二氧化碳气氛下测定各自的半数抑制浓度（IC）值后，将人胶质母细胞瘤U87MG细胞暴露于不同浓度的TMZ、AgNPs和TiONPs中24小时。此后，检测脂质过氧化（丙二醛）、凋亡（半胱天冬酶3、9）、炎症（肿瘤坏死因子-α和白细胞介素-12）和DNA片段化（CAD）的生物标志物。还对GBM进行了吖啶橙/溴化乙锭染色。与单独用TMZ处理的GBM细胞相比，GBM与TMZ和AgNPs或TiONPs联合处理对脂质过氧化（丙二醛）、凋亡（半胱天冬酶3、9）、DNA片段化（CAD）和炎性细胞因子（肿瘤坏死因子-α和白细胞介素-12）的选定生物标志物显示出轻度刺激作用。关于凋亡的显微镜检查结果支持了这些结果。提示药物外排转运蛋白的过表达、凋亡增加、炎症以及药物直接递送至细胞可能有助于增强TMZ与纳米颗粒联合使用时的保护作用。
