In vitro evaluation of Axitinib and Sorafenib treatment in glioblastoma cell viability and morphology.

IF 1.2 4区 医学 Q4 DEVELOPMENTAL BIOLOGY
Alexandru Opriţa, Mihaela Amelia Dobrescu, Elena Victoria Manea, Ştefana Oana Popescu, Ani Simona Sevastre, Andreea Silvia Pîrvu, Iuliana Mihaela Buzatu, Daniela Elise Tache
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引用次数: 1

Abstract

The formation, proliferation, and evolution of glioblastoma (GB) are significantly influenced by pathological angiogenesis. This is supported by several growth factor receptors, such as the vascular endothelial growth factor receptor (VEGFR). In this experiment, we examined how the Food and Drug Administration (FDA) approved VEGFR blockers Sorafenib and Axitinib affect the viability of GB cells in vitro. Cells were cultivated in 96-well culture plates for the experiments, afterwards Sorafenib and Axitinib were administered at doses ranging from 0.3 μM to 80 μM. 2,5-Diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the impact of VEGFR inhibition on high-grade glioma (HGG) cell lines. To observe the morphological changes in cell shape, we used a 10× magnification microscopy. Our results showed that both Axitinib and Sorafenib retarded GB1B culture proliferation in a dose- and time-dependent manner in comparison to control cohorts that had not received any treatment. The half maximal inhibitory concentration (IC50) value for Axitinib was 3.5839 μM after three days of drug administration and 2.2133 μM after seven days of drug administration. The IC50 value for Sorafenib was 3.5152 μM after three days of drug administration and 1.6846 μM after seven days of drug administration. After the treatment with Axitinib or Sorafenib, very few cells became rounded and detached from the support, others remained adherent to the culture substrate, but acquired a larger, flatter shape. Our results indicate that VEGFR might serve as a key target in the treatment of GB. Although it is known that in vitro some drugs block the VEGFR more potently, clinical evidence is required to show whether this actually translates to better clinical outcomes.

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Axitinib和索拉非尼治疗胶质母细胞瘤细胞活力和形态学的体外评估。
胶质母细胞瘤(GB)的形成、增殖和进化受到病理性血管生成的显著影响。这得到了几种生长因子受体的支持,例如血管内皮生长因子受体(VEGFR)。在这个实验中,我们研究了美国食品药品监督管理局(FDA)批准的VEGFR阻断剂索拉非尼和Axitinib如何影响GB细胞的体外生存能力。在96孔培养板中培养细胞进行实验,然后以0.3μM至80μM的剂量给药索拉非尼和Axitinib。2,5-二苯基-2H-溴化四氮唑(MTT)法用于评估VEGFR抑制对高级别胶质瘤(HGG)细胞系的影响。为了观察细胞形状的形态学变化,我们使用了10倍放大显微镜。我们的结果表明,与未接受任何治疗的对照组相比,Axitinib和索拉非尼均以剂量和时间依赖的方式延缓了GB1B培养物的增殖。阿替尼给药3天后的半数最大抑制浓度(IC50)值为3.5839μM,给药7天后为2.2133μM。索拉非尼给药3天后的IC50值为3.5152μM,给药7天后为1.6846μM。在用Axitinib或索拉非尼处理后,很少有细胞变圆并从支持物上分离,其他细胞仍然粘附在培养基上,但获得了更大、更平坦的形状。我们的研究结果表明,VEGFR可能是治疗GB的关键靶点。尽管已知一些药物在体外更有效地阻断VEGFR,但需要临床证据来证明这是否真的能转化为更好的临床结果。
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来源期刊
CiteScore
1.70
自引率
20.00%
发文量
221
审稿时长
3-8 weeks
期刊介绍: Romanian Journal of Morphology and Embryology (Rom J Morphol Embryol) publishes studies on all aspects of normal morphology and human comparative and experimental pathology. The Journal accepts only researches that utilize modern investigation methods (studies of anatomy, pathology, cytopathology, immunohistochemistry, histochemistry, immunology, morphometry, molecular and cellular biology, electronic microscopy, etc.).
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