[1]刘鑫,张宏伟,傅若秋,等.生姜中姜酚类活性成分的抗肿瘤作用及其机制[J].第三军医大学学报,2017,39(09):884-890.
 Liu Xin,Zhang Hongwei,Fu Ruoqiu,et al.Anti-cancer effect of active gingerol ingredients from ginger in vitro and underlying mechanism[J].J Third Mil Med Univ,2017,39(09):884-890.
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生姜中姜酚类活性成分的抗肿瘤作用及其机制(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
39卷
期数:
2017年第09期
页码:
884-890
栏目:
基础医学
出版日期:
2017-05-15

文章信息/Info

Title:
Anti-cancer effect of active gingerol ingredients from ginger in vitro and underlying mechanism
作者:
刘鑫张宏伟傅若秋高宁
第三军医大学药学院生药学教研室
Author(s):
Liu XinZhang HongweiFu RuoqiuGao Ning

Department of Pharmacognosy,College of Pharmacy,Third Military Medical University,Chongqing,400038,China

关键词:
姜酚抗肿瘤提取结构鉴定细胞周期
Keywords:
gingerol anti-cancer extract structure identification cell cycle
分类号:
R282.71; R284.1; R285.5
文献标志码:
A
摘要:

目的      从生姜中提取、分离和鉴定姜酚类物质,初步研究其抗肿瘤作用的分子机制。方法     采用CO2超临界流体对生姜原料进行提取,通过硅胶、RP-C18、Sephadex LH-20和HPLC等色谱方法进行分离和纯化,进而借助MS和NMR等光谱方法鉴定化合物结构,然后采用MTT法检测化合物对不同肿瘤细胞活性的抑制作用,采用流式细胞术及Western blot检测其抑制肿瘤细胞活性的变化。结果     从生姜中提取分离得到5个姜酚类化合物,分别为4,6,8,10-姜酚和5′羟基-6-姜酚。其中8-姜酚和10-姜酚对多种肿瘤细胞的活性均有较好的抑制作用,尤以10-姜酚作用最强,给药72 h后其对乳腺癌MDA-MB-231、MCF-7细胞的IC50分别为(25.80±1.39)、(35.29±2.70)μmol/L。流式细胞术检测发现8-姜酚和10-姜酚可导致乳腺癌细胞的G1期阻滞,其中10姜酚作用于MDA-MB-231和MCF-7细胞24 h后G1期细胞的百分比分别为(66.73±2.93)%、(66.59±2.49)%,相对于对照组的(47.39±1.97)%和(49.17±3.52)%,差异有统计学意义(P<0.01)。Western blot检测结果显示,8-姜酚和10-姜酚可下调MDA-MB-231和MCF-7细胞中G1期相关蛋白Cyclin D1和CDK4的表达;并可降低MAPK信号通路中ERK的磷酸化水平,增强P38的磷酸化水平。结论      从生姜中提取出的8-姜酚和10-姜酚具有明显的抑制肿瘤细胞活性的作用,其机制可能与其影响MAPK通路中ERK、P38磷酸化水平,导致细胞G1期阻滞有关。

Abstract:

Objective      To extract,isolate and identify gingerols from ginger,determine their anti-cancer effect and investigate the underlying mechanism. Methods      Supercritical CO2 fluid extraction was used to extract ginger. The products were then isolated and purified by silica gel,RP-C18,Sephadex LH-20 and high performance liquid chromatography(HPLC),and identified by mass spectrometry(MS) and nuclear magnetic resonance(NMR) spectroscopy. The inhibitory effects of the obtained gingerols on cell proliferation in several cancer cell lines were evaluated by MTT assay. Flow cytometry and Western blotting were employed to determine the cell cycle and the expression of relevant proteins. Results       There were 5 gingerols isolated from ginger,that is,4-gingerol,6-gingerol,8-gingerol,10-gingerol and 5′hydroxy-6-gingerol. Among them,8-gingerol,and especially,10-gingerol exhibited potential inhibitory effects on the cell proliferation in 5 different kinds of cancer cells. The inhibitory concentrations of IC50 were 25.80±1.39 and 35.29±2.70 μmol/L,respectively in the breast cancer MDA-MB-231 and MCF-7 cells after 72 hours’ treatment with 10-gingerol. Flow cytometry found that 8gingerol and 10-gingerol resulted in cell cycle arrest at G1 phase,and the proportion of G1 phase cells was(66.73±2.93)% and(66.59±2.49)%,respectively in the 2 breast cell lines after 10-gingerol treatment for 24 h,significantly higher than in the cells without treatment [(47.39±1.97)%,(49.17±3.52)%,P<0.01]. Western blotting indicated that 8-gingerol and 10-gingerol downregulated the expression levels of G1 phase related proteins,Cyclin D and CDK4 and decreased p-ERK and enhanced p-P38 in MAPK signaling pathway in MDA-MB-231 and MCF-7 cells. Conclusion      8-gingerol and 10-gingerol derived from ginger exhibit obviously inhibitory effects on cancer cell proliferation,which are associated with its interruption of ERK and p38 MAPK signaling pathway and then leading to G1 phase arrest.

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更新日期/Last Update: 2017-05-05