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β-榄香烯增强了川芎嗪对骨肉瘤的抗癌和抗转移作用。

β-elemene enhances anticancer and anti-metastatic effects of osteosarcoma of ligustrazine and .

作者信息

Fang Min, Mei Xiaolong, Yao Hui, Zhang Tao, Zhang Tao, Lu Na, Liu Yanshi, Xu Wenyue, Wan Chunyou

机构信息

Department of Trauma, Tianjin Hospital, Tianjin 300211, P.R. China.

Department of Clinical Medicine, Tianjin Medical University, Tianjin 300270, P.R. China.

出版信息

Oncol Lett. 2018 Mar;15(3):3957-3964. doi: 10.3892/ol.2018.7788. Epub 2018 Jan 12.

Abstract

The present study aimed to determine the anticancer effects of the combination of β-elemene and ligustrazine as well as in . Following evaluation using an MTT assay, β-elemene, ligustrazine and the β-elemene-ligustrazine combination treatments all exhibited the capacity to inhibit the growth of OS-732 cells, with inhibitory rates of 43.3, 54.4, and 75.0%, respectively. Using a flow cytometry assay, it was determined that the β-elemene-ligustrazine combination possessed the highest apoptotic rate (30.6%). Furthermore, β-elemene-ligustrazine combination treatment resulted in the highest downregulation of G protein-coupled receptor 124, vascular endothelial growth factor, matrix metallopeptidase (MMP)-2 and MMP-9 mRNA, and protein expression levels. In addition, the combined treatment led to an increase in the mRNA and protein expression of endostatin, TIMP metallopeptidase inhibitor (TIMP)-1 and TIMP-2 in OS-732 cells. Additionally, β-elemene-ligustrazine caused a decrease in nuclear factor-κB, interleukin-8, C-X-C motif chemokine receptor 4 and urokinase-type plasminogen activator mRNA expression, as well as an increase in caspase-3, caspase-8, and caspase-9 mRNA expression. , the β-elemene-ligustrazine combination was able to reduce the weight and the bulk of the tumor in BALB/c-nu/nu nude mice compared with any other group. All the results described above regarding changes to mRNA and protein expression were further confirmed in the tumor tissue of mice. The results of the present study have suggested that the combination of β-elemene-ligustrazine exhibits greater anticancer effects compared with β-elemene- or ligustrazine-alone treatment.

摘要

本研究旨在确定β-榄香烯与川芎嗪联合使用的抗癌效果以及在……中的效果。通过MTT法评估后,β-榄香烯、川芎嗪及β-榄香烯-川芎嗪联合治疗均表现出抑制OS-732细胞生长的能力,抑制率分别为43.3%、54.4%和75.0%。使用流式细胞术检测确定,β-榄香烯-川芎嗪联合用药的凋亡率最高(30.6%)。此外,β-榄香烯-川芎嗪联合治疗导致G蛋白偶联受体124、血管内皮生长因子、基质金属蛋白酶(MMP)-2和MMP-9的mRNA及蛋白表达水平下调幅度最大。此外,联合治疗使OS-732细胞中内皮抑素、金属蛋白酶组织抑制剂(TIMP)-1和TIMP-2的mRNA及蛋白表达增加。此外,β-榄香烯-川芎嗪使核因子-κB、白细胞介素-8、C-X-C基序趋化因子受体4和尿激酶型纤溶酶原激活剂的mRNA表达降低,同时使半胱天冬酶-3、半胱天冬酶-8和半胱天冬酶-9的mRNA表达增加。与其他任何组相比,β-榄香烯-川芎嗪联合用药能够减轻BALB/c-nu/nu裸鼠肿瘤的重量和体积。上述所有关于mRNA和蛋白表达变化的结果在小鼠肿瘤组织中均得到进一步证实。本研究结果表明,与单独使用β-榄香烯或川芎嗪治疗相比,β-榄香烯-川芎嗪联合使用具有更强的抗癌效果。

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