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长春氟宁与长春瑞滨体外放射增敏及细胞周期效应的比较研究

Comparative study of the radiosensitizing and cell cycle effects of vinflunine and vinorelbine, in vitro.

作者信息

Simoens Cindy, Lardon Filip, Pauwels Bea, De Pooter Christel M J, Lambrechts Hilde A J, Pattyn Greet G O, Breillout Fabienne, Vermorken Jan B

机构信息

Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp (UA/UZA), Wilrijk (Antwerp), Belgium.

出版信息

BMC Cancer. 2008 Feb 29;8:65. doi: 10.1186/1471-2407-8-65.

Abstract

BACKGROUND

Vinca alkaloids are an important class of anticancer agents and semisynthetic vinca alkaloids are developed to improve the therapeutic index of this class of drugs. In the present study, a direct comparison was made between vinflunine and vinorelbine regarding their radiosensitizing and cell cycle effects.

METHODS

Four human tumour cell lines were tested under identical experimental conditions, using equitoxic concentrations of vinflunine and vinorelbine.

RESULTS

Vinflunine and vinorelbine induced a comparable radiosensitizing effect (p-value never below 0.01) when cells were incubated for 24 h immediately prior to radiation. Regarding the cell cycle effects, a statistically significant concentration-dependent G2/M block was seen after 24 h incubation with vinorelbine in all tested cell lines. Similar results, with small cell line-related differences, were observed with vinflunine.

CONCLUSION

The radiosensitizing effects of both semisynthetic vinca alkaloids were comparable (not statistically different) and nearly always cell line-specific and concentration-dependent. The cell cycle effects could be related to the observed radiosensitizing effects. Considering the more favourable toxicity profile of vinflunine, this agent might be more promising than vinorelbine for chemoradiation studies in the clinic.

摘要

背景

长春花生物碱是一类重要的抗癌药物,半合成长春花生物碱的研发旨在提高这类药物的治疗指数。在本研究中,对长春氟宁和长春瑞滨的放射增敏作用及细胞周期效应进行了直接比较。

方法

在相同实验条件下,使用长春氟宁和长春瑞滨的等效毒性浓度对四种人类肿瘤细胞系进行检测。

结果

当在放疗前立即将细胞孵育24小时时,长春氟宁和长春瑞滨诱导出相当的放射增敏作用(p值从未低于0.01)。关于细胞周期效应,在所有测试细胞系中,与长春瑞滨孵育24小时后均观察到具有统计学意义的浓度依赖性G2/M期阻滞。长春氟宁也观察到类似结果,只是不同细胞系之间存在细微差异。

结论

两种半合成长春花生物碱的放射增敏作用相当(无统计学差异),且几乎总是细胞系特异性和浓度依赖性的。细胞周期效应可能与观察到的放射增敏作用有关。鉴于长春氟宁具有更有利的毒性特征,在临床放化疗研究中,该药物可能比长春瑞滨更具前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d7e/2311317/f413786acacd/1471-2407-8-65-1.jpg

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