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二烯丙基三硫醚逆转人骨肉瘤细胞系中 P-糖蛋白介导的多药耐药性。

Reversion of P-glycoprotein-mediated multidrug resistance by diallyl trisulfide in a human osteosarcoma cell line.

机构信息

Department of Emergency Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.

Department of Urinary Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.

出版信息

Oncol Rep. 2014 Jun;31(6):2720-6. doi: 10.3892/or.2014.3154. Epub 2014 Apr 24.

DOI:10.3892/or.2014.3154
PMID:24788927
Abstract

Diallyl trisulfide (DATS), the main sulfuric compound in garlic, has been shown to have antitumor effects. The present study aimed to ascertain whether DATS reverses the drug resistance of human osteosarcoma cells in vitro and to investigate its potential mechanisms. Human osteosarcoma U2-OS cells were treated with different concentrations of DATS. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while P-glycoprotein (P-gp) expression and the proportion of apoptotic cells were measured by flow cytometry. Morphological changes were observed under an optical microscope. Νuclear factor-κB (NF-κB) and inhibitor of NF-κB (IκB) activities were measured by PCR and western blot analysis. Results showed that the proliferation of U2-OS cells treated with different concentrations of DATS was significantly decreased in a concentration- and time-dependent manner. DATS increased the toxic effect of adriamycin on U2-OS cells. Moreover, P-gp expression was decreased and the apoptosis rate was increased in a concentration-dependent manner following treatment of DATS. Additionally, NF-κB activity was inhibited by DATS while expression of IκB was increased. Our data clearly suggest that DATS has significant anticancer effects on human osteosarcoma cells. The potential mechanisms include reducing the multidrug resistance and inducing apoptosis. NF-κB suppression may be involved in DATS-induced inhibition of cell proliferation.

摘要

二烯丙基三硫醚(DATS)是大蒜中的主要含硫化合物,已被证明具有抗肿瘤作用。本研究旨在确定 DATS 是否能逆转人骨肉瘤细胞的体外耐药性,并探讨其潜在机制。用人骨肉瘤 U2-OS 细胞进行不同浓度 DATS 的处理。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定法来测量细胞增殖,通过流式细胞术来测量 P-糖蛋白(P-gp)表达和凋亡细胞的比例。在光学显微镜下观察形态变化。通过 PCR 和 Western blot 分析来测量核因子-κB(NF-κB)和 NF-κB 抑制剂(IκB)的活性。结果表明,用不同浓度 DATS 处理的 U2-OS 细胞的增殖以浓度和时间依赖的方式显著降低。DATS 增加了阿霉素对 U2-OS 细胞的毒性作用。此外,DATS 处理后 P-gp 表达降低,凋亡率呈浓度依赖性增加。此外,NF-κB 活性被 DATS 抑制,而 IκB 的表达增加。我们的数据清楚地表明,DATS 对人骨肉瘤细胞具有显著的抗癌作用。潜在的机制包括降低多药耐药性和诱导细胞凋亡。NF-κB 抑制可能参与 DATS 诱导的细胞增殖抑制。

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