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标准化槲寄生(欧洲槲寄生)制剂与曲妥珠单抗体外抗肿瘤作用的相互作用。

Interaction of a standardized mistletoe (Viscum album) preparation with antitumor effects of Trastuzumab in vitro.

作者信息

Weissenstein U, Kunz M, Urech K, Regueiro U, Baumgartner S

机构信息

Iscador AG, Arlesheim, Switzerland.

Institute of Integrative Medicine, Witten/Herdecke University, Herdecke, Germany.

出版信息

BMC Complement Altern Med. 2016 Aug 4;16:271. doi: 10.1186/s12906-016-1246-2.

Abstract

BACKGROUND

Besides conventional anticancer therapy many breast cancer patients use complementary and alternative medicine (CAM) like the medicinal herb mistletoe (Viscum album L.). To gain more knowledge about possible herb-drug interactions between CAM and conventional anticancer medications, in the present in vitro study we investigated the effect of a standardized mistletoe preparation on the action of Trastuzumab, a drug used for the treatment of Her-2 positive breast cancer.

METHODS

The Her-2 positive human breast carcinoma cell line SK-BR-3 was treated with Trastuzumab. Different doses of the drug were combined with Viscum album extract (VAE) in clinically relevant doses. Proliferation, apoptosis, cell cycle and the secretion of vascular endothelial growth factor (VEGF) were analyzed.

RESULTS

No inhibition of antitumor efficacy of Trastuzumab by VAE was detected. VAE and Trastuzumab, either alone or in combination, inhibited proliferation of SK-BR-3 cells in vitro. At higher concentrations VAE induced apoptosis, which was not observed for Trastuzumab. Cells treated with Trastuzumab underwent a G0/G1 cell cycle arrest and cells treated with VAE a G2/M arrest. After application of the two drugs in combination both G0/G1 and G2/M arrest was observed. VEGF secretion of SK-BR-3 cells was significantly inhibited by sole treatment with Trastuzumab or VAE. Combined treatment of Trastuzumab and VAE at clinically relevant doses showed additive inhibitory effects on VEGF secretion.

CONCLUSIONS

VAE did not interfere with cytostatic effects of Trastuzumab on SK-BR-3 cells in vitro. Our in vitro results suggest that no risk of safety by herb drug interactions has to be expected from the exposition of cancer cells to Trastuzumab and VAE simultaneously. In contrast, VAE and Trastuzumab seem to exhibit complementary anti-cancer effects in vitro.

摘要

背景

除了传统的抗癌治疗外,许多乳腺癌患者还使用补充和替代医学(CAM),如药用植物槲寄生(欧洲槲寄生)。为了更多地了解CAM与传统抗癌药物之间可能存在的草药-药物相互作用,在本体外研究中,我们研究了标准化槲寄生制剂对曲妥珠单抗(一种用于治疗Her-2阳性乳腺癌的药物)作用的影响。

方法

用曲妥珠单抗处理Her-2阳性人乳腺癌细胞系SK-BR-3。将不同剂量的该药物与临床相关剂量的欧洲槲寄生提取物(VAE)联合使用。分析了细胞增殖、凋亡、细胞周期以及血管内皮生长因子(VEGF)的分泌情况。

结果

未检测到VAE对曲妥珠单抗抗肿瘤疗效的抑制作用。VAE和曲妥珠单抗单独或联合使用均能在体外抑制SK-BR-3细胞的增殖。在较高浓度下,VAE诱导细胞凋亡,而曲妥珠单抗未观察到这种现象。用曲妥珠单抗处理的细胞发生G0/G1期细胞周期阻滞,用VAE处理的细胞发生G2/M期阻滞。联合应用两种药物后,观察到G0/G1期和G2/M期阻滞。单独用曲妥珠单抗或VAE处理可显著抑制SK-BR-3细胞的VEGF分泌。曲妥珠单抗和VAE在临床相关剂量下联合治疗对VEGF分泌具有相加抑制作用。

结论

VAE在体外不干扰曲妥珠单抗对SK-BR-3细胞的细胞抑制作用。我们的体外研究结果表明,癌细胞同时暴露于曲妥珠单抗和VAE时,无需预期存在草药-药物相互作用导致的安全风险。相反,VAE和曲妥珠单抗在体外似乎表现出互补的抗癌作用。

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