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阿柏西普和三氧化二砷对体外口腔鳞状细胞癌增殖、迁移和凋亡的影响。

The effect of aflibercept and arsenic trioxide on the proliferation, migration and apoptosis of oral squamous cell carcinoma in vitro.

机构信息

Oral and Maxillofacial Pathology Department, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.

School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Mol Biol Rep. 2021 Apr;48(4):3223-3235. doi: 10.1007/s11033-021-06341-w. Epub 2021 Apr 30.

DOI:10.1007/s11033-021-06341-w
PMID:33929648
Abstract

Aflibercept and arsenic trioxide drugs apply a cytotoxic effect on some human cancer cell lines. However, no more study has followed the effects of both drugs, especially arsenic trioxide, on oral squamous cell carcinoma (OCC). We used three OCC lines as a model to show the effect of these drugs on the genetically complex disease and investigate its targeted therapy. In this study, three human OCC cell lines were used from different patients. We treated cell lines with both medications to detect the effect and relevant molecular basis. First, methyl thiazolyl tetrazolium (MTT) assay was performed to detect the cytotoxicity effect and cell growth. Second, flow cytometry, gene and protein expression were performed to evaluate the anti-angiogenic effect on OCC lines. Next apoptosis was analyzed by flow cytometry. Finally, clonogenesis capacity and cell migration were assessed by colony formation assay and wound healing, respectively. Aflibercept had no cytotoxic effect on the three OCC cell lines but decreased cell growth rate. Arsenic trioxide had a significant cytotoxic effect on three cell lines. Our results demonstrated that both drugs significantly decreased endoglin, VEGFA, and VEGFB expression. In addition, Migration and colony formation assays confirmed that these drugs have significant anti-proliferative and anti-migration effect on oral carcinoma cells. These results revealed that both medications might be a potential drug for the management of oral cancer patients.

摘要

阿柏西普和三氧化二砷药物对一些人类癌细胞系具有细胞毒性作用。然而,没有更多的研究关注这两种药物(尤其是三氧化二砷)对口腔鳞状细胞癌(OCC)的影响。我们使用三种 OCC 细胞系作为模型,以展示这些药物对这种遗传复杂疾病的影响,并研究其靶向治疗。在这项研究中,我们使用了来自不同患者的三种人类 OCC 细胞系。我们用这两种药物处理细胞系,以检测其效果及其相关的分子基础。首先,进行甲基噻唑基四唑(MTT)测定以检测细胞毒性作用和细胞生长。其次,通过流式细胞术、基因和蛋白质表达来评估对 OCC 细胞系的抗血管生成作用。接下来,通过流式细胞术分析细胞凋亡。最后,通过集落形成测定和划痕愈合分别评估克隆形成能力和细胞迁移。阿柏西普对三种 OCC 细胞系没有细胞毒性作用,但降低了细胞生长速率。三氧化二砷对三种细胞系均有显著的细胞毒性作用。我们的结果表明,这两种药物均显著降低了内胚层蛋白、VEGFA 和 VEGFB 的表达。此外,迁移和集落形成测定证实,这些药物对口腔癌细胞具有显著的增殖抑制和迁移抑制作用。这些结果表明,这两种药物可能是治疗口腔癌患者的潜在药物。

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本文引用的文献

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Intratumor genetic heterogeneity in squamous cell carcinoma of the oral cavity.口腔鳞状细胞癌的肿瘤内基因异质性
Head Neck. 2019 Aug;41(8):2514-2524. doi: 10.1002/hed.25719. Epub 2019 Mar 14.
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Downregulation of Semaphorin-3F is associated with poor prognostic significance in osteosarcoma patients.信号素-3F的下调与骨肉瘤患者的预后不良相关。
Am J Cancer Res. 2016 Oct 1;6(10):2252-2262. eCollection 2016.
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Endoglin (CD105) and microvessel density in oral squamous cell carcinoma.口腔鳞状细胞癌中的内皮糖蛋白(CD105)与微血管密度
阿帕替尼与人参皂甙 Rb1 协同抑制下咽癌细胞生长。
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Arsenic trioxide induces apoptosis via the mitochondrial pathway by upregulating the expression of Bax and Bim in human B cells.三氧化二砷通过上调人B细胞中Bax和Bim的表达,经由线粒体途径诱导细胞凋亡。
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