The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Cell Mol Biol (Noisy-le-grand). 2024 Jun 5;70(6):211-216. doi: 10.14715/cmb/2024.70.6.32.
This study investigated the regulatory impact of Toll-like receptor 4 (TLR4) gene on glioma cell proliferation and apoptosis, elucidating the molecular mechanisms underlying TLR4-induced growth inhibition in vivo. U-87MG-Sh and U-87MG-NC cells, with silenced TLR4 and negative control plasmid respectively, were established. Eighteen nude mice, divided into transfection, negative control, and blank control groups, were inoculated with corresponding cells. Over four weeks, the transfection group exhibited significantly reduced tumor growth rates, smaller mass and volume, and lower growth activity compared to controls. Histological analysis revealed sparse tumor cells, increased fibrous connective tissue, and slower angiogenesis in the transfection group. Flow cytometry demonstrated a lower proliferation index and increased G0/1 cell count in the transfection group. mRNA levels of TLR4, NF-κB, and CyclinD1 were significantly lower in the transfection group. TLR4 silencing correlated with U-87MG cell proliferation regulation, growth inhibition, NF-κB and CyclinD1 modulation, and induction of cell cycle arrest and apoptosis. These findings suggest TLR4 as a potential gene therapy target for glioma.
本研究探讨了 Toll 样受体 4（TLR4）基因对神经胶质瘤细胞增殖和凋亡的调控作用，阐明了 TLR4 诱导体内生长抑制的分子机制。构建了 TLR4 沉默的 U-87MG-Sh 细胞和阴性对照质粒转染的 U-87MG-NC 细胞。将 18 只裸鼠分为转染组、阴性对照组和空白对照组，分别接种相应的细胞。四周后，与对照组相比，转染组肿瘤生长速度明显降低，肿瘤质量和体积减小，生长活性降低。组织学分析显示，转染组肿瘤细胞稀疏，纤维结缔组织增加，血管生成速度较慢。流式细胞术显示转染组细胞增殖指数降低，G0/1 期细胞计数增加。转染组 TLR4、NF-κB 和 CyclinD1 的 mRNA 水平显著降低。TLR4 沉默与 U-87MG 细胞增殖调控、生长抑制、NF-κB 和 CyclinD1 调节以及诱导细胞周期阻滞和凋亡有关。这些发现表明 TLR4 可能成为神经胶质瘤的潜在基因治疗靶点。
