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倍他司汀对不同来源细胞系的生理作用。

Physiological Effects of Betahistine on Cell Lines of Various Origins.

作者信息

Kepekçi Ahmet Hamdi, Gündoğan Gül İpek, Kıg Cenk

机构信息

Istanbul Yeni Yuzyil University Health Vocational School, Divison of Audiometry, Istanbul, Turkey

Istanbul Yeni Yuzyil University Faculty of Medicine, Department of Histology and Embryology, Istanbul, Turkey

出版信息

Turk J Pharm Sci. 2021 Apr 20;18(2):140-145. doi: 10.4274/tjps.galenos.2020.88155.

Abstract

OBJECTIVES

Betahistine is a histamine analog commonly prescribed for symptomatic treatment of vertiginous symptoms. studies have shown that betahistine was not toxic at the prescribed doses in a nasal epithelial cell line. However, the effect of betahistine on other cell types has not been studied. In this study, we aimed to investigate some of the physiological effects of betahistine on L929 fibroblast, A549 lung cancer, human umbilical vein endothelial (HUVEC), and Ishikawa endometrial cell lines.

MATERIALS AND METHODS

Cellular proliferation was assed assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis was evaluated by acridine orange-ethidium bromide staining, and cellular migration was assed assessed by scratch assay.

RESULTS

Betahistine treatment (0.1-0.5 mg/mL, 24 hours) can inhibit cell proliferation and induce apoptosis in HUVEC, A549, Ishikawa, and L929 cell lines. Betahistine (≥0.1 mg/mL) significantly increased the number of apoptotic cells (HUVEC: 26.3%, A549: 17.3%, L929: 8.6%, and Ishikawa: 2.3%). Betahistine at doses over 0.1 mg/mL significantly suppressed the cell migration rate in all of the cell lines. In contrast, exposure to a low dose of betahistine (0.025 mg/mL) induced migration rates of HUVEC and Ishikawa cells by 81% and 48%, respectively.

CONCLUSION

Betahistine may alter the processes of cellular proliferation, apoptosis, and cellular migration in a cell line- and dose-dependent manner. In this sense, proliferative and metastatic properties of certain cancer cells can potentially be altered in response to betahistine treatment.

摘要

目的

倍他司汀是一种组胺类似物,常用于眩晕症状的对症治疗。研究表明,在规定剂量下,倍他司汀对鼻上皮细胞系无毒。然而,倍他司汀对其他细胞类型的影响尚未得到研究。在本研究中,我们旨在研究倍他司汀对L929成纤维细胞、A549肺癌细胞、人脐静脉内皮细胞(HUVEC)和石川子宫内膜细胞系的一些生理作用。

材料与方法

通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法评估细胞增殖,通过吖啶橙-溴化乙锭染色评估细胞凋亡,并通过划痕试验评估细胞迁移。

结果

倍他司汀处理(0.1 - 0.5 mg/mL,24小时)可抑制HUVEC、A549、石川和L929细胞系的细胞增殖并诱导细胞凋亡。倍他司汀(≥0.1 mg/mL)显著增加凋亡细胞数量(HUVEC:26.3%,A549:17.3%,L929:8.6%,石川:2.3%)。剂量超过0.1 mg/mL的倍他司汀显著抑制所有细胞系的细胞迁移率。相比之下,低剂量倍他司汀(0.025 mg/mL)分别使HUVEC和石川细胞的迁移率提高了81%和48%。

结论

倍他司汀可能以细胞系和剂量依赖性方式改变细胞增殖、凋亡和细胞迁移过程。从这个意义上说,某些癌细胞的增殖和转移特性可能会因倍他司汀治疗而发生潜在改变。

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Histamine receptors and cancer pharmacology: an update.组胺受体与癌症药理学:最新进展。
Br J Pharmacol. 2020 Feb;177(3):516-538. doi: 10.1111/bph.14535. Epub 2018 Dec 13.
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21st Century Cell Culture for 21st Century Toxicology.21世纪毒理学的21世纪细胞培养。
Chem Res Toxicol. 2017 Jan 17;30(1):43-52. doi: 10.1021/acs.chemrestox.6b00269. Epub 2016 Dec 5.
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Betahistine for symptoms of vertigo.倍他司汀用于治疗眩晕症状。
Cochrane Database Syst Rev. 2016 Jun 21;2016(6):CD010696. doi: 10.1002/14651858.CD010696.pub2.
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Use of betahistine in the treatment of peripheral vertigo.倍他司汀在周围性眩晕治疗中的应用。
Acta Otolaryngol. 2015;135(12):1205-11. doi: 10.3109/00016489.2015.1072873. Epub 2015 Aug 6.

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