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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >Betulinic Acid Derivatives NVX-207 and B10 for Treatment of Glioblastoma—An in Vitro Study of Cytotoxicity and Radiosensitization
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Betulinic Acid Derivatives NVX-207 and B10 for Treatment of Glioblastoma—An in Vitro Study of Cytotoxicity and Radiosensitization

机译：桦木酸衍生物NVX-207和B10用于治疗胶质母细胞瘤的细胞毒性和放射增敏作用的体外研究

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Betulinic acid (BA), a pentacyclic triterpene, represents a new therapeutic substance that has potential benefits for treating glioblastoma. Recently, new strategies for producing BA derivatives with improved properties have evolved. However, few studies have examined the combination of BA or BA derivatives using radiotherapy. The effects of two BA derivatives, NVX-207 and B10, on cellular and radiobiological behavior were analyzed using glioblastoma cell lines (U251MG, U343MG and LN229). Based on IC50 values under normoxic conditions, we detected a 1.3–2.9-fold higher cytotoxicity of the BA derivatives B10 and NVX-207, respectively, compared to BA. Incubation using both BA derivatives led to decreased cell migration, cleavage of PARP and decreased protein expression levels of Survivin. Weak radiation sensitivity enhancement was observed in U251MG cells after treatment with both BA derivatives. The enhancement factors at an irradiation dose of 6 Gy after treatment with 5 µM NVX-207 and 5 µM B10 were 1.32 (p = 0.029) and 1.55 (p = 0.002), respectively. In contrast to BA, neither NVX-207 nor B10 had additional effects under hypoxic conditions. Our results suggest that the BA derivatives NVX-207 and B10 improve the effects of radiotherapy on human malignant glioma cells, particularly under normoxic conditions.
机译：五环三萜烯桦木酸（BA）代表一种新的治疗性药物，对胶质母细胞瘤具有潜在的益处。近来，已经开发出生产具有改善的性能的BA衍生物的新策略。但是，很少有研究使用放射疗法检查BA或BA衍生物的组合。使用胶质母细胞瘤细胞系（U251MG，U343MG和LN229）分析了两种BA衍生物NVX-207和B10对细胞和放射生物学行为的影响。根据常氧条件下的IC50值，我们发现BA衍生物B10和NVX-207的细胞毒性分别比BA高1.3-2.9倍。使用两种BA衍生物进行孵育都会导致细胞迁移减少，PARP裂解以及Survivin蛋白质表达水平降低。两种BA衍生物处理后，在U251MG细胞中均观察到弱的辐射敏感性增强。在用5 µM NVX-207和5 µM B10处理后，在6 Gy的辐射剂量下增强因子分别为1.32（p = 0.029）和1.55（p = 0.002）。与BA相反，NVX-207和B10在缺氧条件下均没有其他作用。我们的结果表明，BA衍生物NVX-207和B10改善了放射疗法对人恶性神经胶质瘤细胞的作用，尤其是在常氧条件下。

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