[1]任海玉,孙剑经,李 多,等.姜黄素通过Wnt2/β-catenin通路逆转食管癌Eca-109/VCR细胞多药耐药性研究[J].中国药理学通报,2018,(10):1455-1460.[doi:10.3969/j.issn.1001-1978.2018.10.025]
 REN Hai-yu,SUN Jian-jing,LI Duo,et al.Curcumin reversed multi-drug resistance of esophageal carcinoma in Eca-109/VCR cell line through Wnt2/β-catenin pathway[J].Chinese Pharmacological Bulletin,2018,(10):1455-1460.[doi:10.3969/j.issn.1001-1978.2018.10.025]
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姜黄素通过Wnt2/β-catenin通路逆转食管癌Eca-109/VCR细胞多药耐药性研究()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年10期
页码:
1455-1460
栏目:
论著
出版日期:
2018-09-26

文章信息/Info

Title:
Curcumin reversed multi-drug resistance of esophageal carcinoma in Eca-109/VCR cell line through Wnt2/β-catenin pathway
文章编号:
1001-1978(2018)10-1455-06
作者:
任海玉1孙剑经2李 多2牛树荣1刘 华3罗 强3张林西3
河北北方学院1.研究生学院、2.附属第一医院消化内科、3.生命科学研究中心,河北 张家口 075000
Author(s):
REN Hai-yu1 SUN Jian-jing2LI Duo2NIU Shu-rong1LIU Hua3LUO Qiang3ZHANG Lin-xi3
1.Postgraduate School of Hebei North University; 2.Digestion Dept,1st Affiliated Hospital,Hebei North University; 3.Life Science Research Centre of Hebei North University,Zhangjiakou 075000,China
关键词:
食管癌 Wnt2/β-catenin通路 姜黄素 长春新碱 多药耐药 实时荧光定量PCR
Keywords:
esophageal carcinoma Wnt2/β-catenin pathway curcumin vincristine multi-drug resistance qRT-PCR
分类号:
R282.71; R329.24; R735.102.2; R735.105; R915; R977.6
DOI:
10.3969/j.issn.1001-1978.2018.10.025
文献标志码:
A
摘要:
目的 研究姜黄素(curcumin,Cur)对人食管癌耐药细胞株Eca-109/VCR多药耐药的逆转作用,并探讨其可能的逆转机制。方法 CCK-8法检测不同浓度Cur和VCR对Eca-109/VCR细胞增殖的影响,以及Cur(20 μmol·L-1)对Eca-109/VCR细胞多药耐药的逆转作用; FCM检测细胞凋亡率; ELISA法检测P-gp蛋白的表达水平; 实时荧光定量PCR分析Wnt2、β-catenin mRNA的相对表达量; Western blot检测Wnt2、β-catenin、MMP-2、HMGB1的蛋白表达水平。结果 随着Cur浓度的增加,细胞抑制率逐渐升高,呈剂量依赖性。Cur(20 μmol·L-1)与不同浓度VCR联合作用可明显提高细胞增殖抑制率,逆转倍数为3.49。Cur(20 μmol·L-1)与VCR(2.0 mg·L-1)联合作用可明显提高细胞凋亡率,降低P-gp蛋白含量,下调Wnt2、β-catenin mRNA的相对表达,并抑制Wnt2、β-catenin、MMP-2、HMGB1蛋白的表达。结论 Cur具有逆转食管癌细胞多药耐药的作用,其作用机制可能与下调Wnt2、β-catenin的表达,抑制Wnt2/β-catenin通路活性,以及下调侵袭相关蛋白MMP-2、HMGB1的表达有关。
Abstract:
Aim To study the reversal effect of curcumin(Cur)on vincristine(VCR)-resistance in human esophageal carcinoma Eca-109/VCR cells as well as its mechanism.Methods The esophageal carcinoma drug-resistant Eca-109/VCR cells were treated with different concentrations of Cur and VCR.The proliferation of Eca-109/VCR cells were detected by CCK-8 assay,and the concentration of Cur screened by CCK-8 assay.The apoptosis rate was detected by flow cytometry(FCM).The level of P-glycoprotein(P-gp)was measured by enzyme-linked-immunosorbent assay(ELISA).The level of Wnt2 and β-catenin mRNA were detected by quantitative real-time polymerase chain reaction.The relative protein expressions ofWnt2,β-catenin,MMP-2 and HMGB1 were analyzed by Western blot.Results The proliferation inhibitory rates were positively correlated with the concentration of curcumin,in a dose-dependent manner.The combination of Cur(20 μmol·L-1)and different concentrations of VCR could significantly increase the proliferation inhibitory rates of cells.The drug-resistant reversal fold was 3.49.The combination of Cur(20 μmol·L-1)and VCR(2.0 mg·L-1)could markedly increase the apoptosis ratios of cells,reduce the protein expression of P-gp,down-regulate the level of Wnt2 and β-catenin mRNA,and decrease the relative protein level of Wnt2,β-catenin,MMP-2 and HMGB1.Conclusions Cur can reverse multi-drug resistance of Eca-109/VCR cells.The mechanism may be related to the down-regulation of Wnt2 and β-catenin,which can inhibit the activity of Wnt2/β-catenin pathway.The down-regulation of MMP-2 and HMGB1 may also be one of the possible mechanisms.

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备注/Memo

备注/Memo:
收稿日期:2018-05-16,修回日期:2018-07-26
基金项目:河北省自然科学基金资助项目(No H2014405033); 河北北方学院自然科学课题项目(No ZD201414)
作者简介:任海玉(1990-),女,硕士生,研究方向:消化道肿瘤,E-mail: 15731333630@163.com;
张林西(1968-),男,博士,教授,研究方向:消化道肿瘤病因、病理学,通讯作者,E-mail:zlxwxl@163.com
更新日期/Last Update: 2018-08-26