胶质母细胞瘤是一种高度恶性的脑肿瘤，预后不良。传统的治疗方法由于对正常组织的毒性影响和肿瘤细胞耐药性的发展而存在局限性。本研究旨在通过靶向血管生成探索胶质母细胞瘤治疗的替代机制。该研究调查了肝素在胶质母细胞瘤治疗中的抗血管生成特性。为了克服肝素的局限性，通过将肝素与牛磺酸结合来合成一种肝素-牛磺酸共轭物（LHT7）。该研究利用U87MG人类胶质母细胞瘤细胞系和人脐静脉内皮细胞（HUVEC）作为实验模型。进行了细胞活力测定和分株实验来评估LHT7的作用。此外，还测量了血管生成相关蛋白（如磷酸化ERK和磷酸化VEGFR2）的磷酸化。通过胶质母细胞瘤原位小鼠模型进一步评估了LHT7的抗血管生成效应。 与U87MG人类胶质母细胞瘤细胞相比，LHT7的处理导致细胞存活率的剂量依赖性降低。LHT7处理明显降低了HUVEC细胞的分枝。此外，LHT7处理导致血管生成相关蛋白（包括磷酸化ERK和磷酸化VEGFR2）的磷酸化减少。在胶质母细胞瘤原位小鼠模型中，LHT7展示了抗血管生成效应，支持其作为治疗剂的潜力。 通过胶质母细胞瘤中肝素和牛磺酸的共轭，创造了LHT7，相对于传统的胶质母细胞瘤治疗方法具有几个优点。LHT7表现出了抗血管生成特性，如细胞存活率的降低和内皮细胞分枝的抑制。此外，LHT7调控了血管生成相关蛋白的磷酸化。这些发现表明，LHT7作为胶质母细胞瘤治疗药物具有潜力，并为改善患者预后提供了潜在的影响。© 2023年. 美国生物材料学学会.

Glioblastoma is a highly malignant brain tumor associated with poor prognosis. Conventional therapeutic approaches have limitations due to their toxic effects on normal tissue and the development of tumor cell resistance. This study aimed to explore alternative mechanisms for glioblastoma treatment by targeting angiogenesis.The study investigated the anti-angiogenic properties of heparin in glioblastoma treatment. To overcome the limitations of heparin, a heparin-taurocholate conjugate (LHT7) was synthesized by conjugating heparin to taurocholic acid. The study utilized the U87MG human glioblastoma cell line and human umbilical vein endothelial cells (HUVEC) as experimental models. Cell viability assays and sprouting assays were performed to assess the effects of LHT7. Additionally, phosphorylation of angiogenesis-related proteins, such as phospho-ERK and phospho-VEGFR2, was measured. The anti-angiogenic effects of LHT7 were further evaluated using a glioblastoma orthotopic mouse model.Treatment with LHT7 resulted in a dose-dependent reduction in cell viability in U87MG human glioblastoma cells. The sprouting of HUVEC cells was significantly decreased upon LHT7 treatment. Furthermore, LHT7 treatment led to a decrease in the phosphorylation of angiogenesis-related proteins, including phospho-ERK and phospho-VEGFR2. In the glioblastoma orthotopic mouse model, LHT7 exhibited anti-angiogenic effects, supporting its potential as a therapeutic agent.The conjugation of heparin and taurocholic acid to create LHT7 offers several advantages over conventional therapeutic approaches for glioblastoma. LHT7 demonstrated anti-angiogenic properties, as evidenced by the reduction in cell viability and inhibition of endothelial cell sprouting. Moreover, LHT7 modulated the phosphorylation of angiogenesis-related proteins. These findings suggest that LHT7 holds promise as a medication for glioblastoma treatment, offering potential implications for improving patient outcomes.© 2023. The Korean Society for Biomaterials.