姜黄素对人食管癌Eca-109/VCR细胞多药耐药性的逆转作用  

Curcumin reverses multidrug resistance of human esophageal cancer Eca-109/VCR cells

作　　者：孙晓冉[1] 孙剑经[2] 田若楠 刘华[3] 罗强[3] 张晓丽[3] 张林西[3] SUN Xiaoran Sun Jianjing TIAN Ruonan LIU Hua LUO Qiang ZHANG Xiaoli ZHANG Linxi(Department of Postgraduate, Hebei North University, Zhangjiakou 075000, Hebei Province, China Department of Gastroenterology, Ftrst Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei Province, China Department of Pathology, Life Science Research Center of Hebei North University, Zhang, jiakou 075000, Hebei Province, China)

机构地区：[1]河北北方学院研究生部,河北张家口075000 [2]河北北方学院附属第一医院消化内科,河北张家口075000 [3]河北北方学院生命科学研究中心病理教研室,河北张家口075000

出　　处：《肿瘤》2016年第12期1312-1319,共8页Tumor

基　　金：河北省自然科学基金(编号:H2014405033);河北北方学院自然科学研究计划项目(编号:ZD201414)~~

摘　　要：目的 :探讨姜黄素(curcumin,Cur)对人食管癌耐长春新碱(vincristine,VCR)Eca-109/VCR细胞株多药耐药的逆转作用及可能的作用机制。方法 :CCK-8法检测不同浓度VCR对亲本Eca-109细胞和耐药Eca-109/VCR细胞增殖的影响,以及Cur(20μmol/L)对Eca-109/VCR细胞多药耐药的逆转作用;FCM法检测Cur(20μmol/L)联合VCR(2μg/m L)作用6、12和24 h时对Eca-109/VCR细胞凋亡率的影响;实时荧光定量PCR法分析Eca-109/VCR细胞中多药耐药1(multiple drug resistance 1,MDR1)m RNA的表达;免疫细胞化学法检测Eca-109/VCR细胞中P-糖蛋白(P-glycoprotein,P-gp)及多药耐药相关蛋白(multidrug resistancerelated protein,MRP)的表达。结果 :Cur(20μmol/L)作用于Eca-109/VCR细胞24 h时,细胞的增殖抑制率为(8.08±0.23)%;VCR对Eca-109和Eca-109/VCR细胞的半数抑制浓度(half maximal inhibitory concentration,IC50)分别为0.157和2.524μg/mL;Cur(20μmol/L)与不同浓度的VCR联合作用后,Eca-109/VCR细胞对VCR的逆转耐药倍数为3.58。Cur(20μmol/L)联合VCR(2μg/mL)作用于Eca-109/VCR细胞12和24 h后,细胞凋亡率分别为(11.27±0.21)%和(18.77±0.26)%,较VCR单药组明显提高(P值均<0.05);Cur(20μmol/L)与VCR(2μg/m L)或VCR(3μg/m L)联合作用于Eca-109/VCR细胞24 h后,MDR1 m RNA表达率均明显降低(P值均<0.05);Cu(r20μmol/L)与VCR联合作用24 h后,Eca-109/VCR细胞中的P-gp和MRP阳性表达率均较VCR单药组明显下降(P值均<0.05)。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P-gp和MRP的表达有关。Objective： To investigate the reversal effect of curcumin （Cur） on multidrug resistance of human esophageal cancer vincristine （VCR）- resistant Eca-IO9/VCR cells, and to explore its possible mechanism.Methods： The effects of different concentrations of VCR on the proliferation of parental Eca-109 cells and VCR-resistant Eca-109/VCR cells, as well as the reversal effect of Cur combined with VCR on multidrug resistance of Eca-109/VCR cells were detected by CCK-8 method. The apoptosis rates of Eca-109/VCR cells after treatment with Cur （20μmol/L） combined with VCR （2μg/mL） for 6, 12 or 24 h were detected by FCM. The expression level of multiple drug resistance 1 （MDR1） mRNA in Eca-109/VCR cells was measured by real-time fluorescent quantitative PCR. The expression levels of P-glycoprotein （P-gp） and multidrug resistance-related protein （MRP） were detected by immunocytochemistry. Results： The proliferation inhibitory rates of Eca-109/VCR cells were （8.08___0.23）% after treatment with 20μmol/L Cur for 24 h. The half inhibitory concentration （IC50） of VCR was 0.157 and 2.524μg/mL in Eca-109 cells and Eca-IO9/VCR cells, respectively. After treatment with Cur （20μmol/L） combined with various concentrations of VCR, the drug-resistant reversal fold was 3.58 in Eca-109/VCR cells. After treatment with Cur （20 μmol/L） combined with VCR （2μg/mL） for 12 and 24 h, the apoptosis rates of Eca-109/VCR cells were （11.27±0.21）% and （18.77±0.26）%, which were higher than that in VCR （2 μg/mL） group （both P 〈 0.05）. After treatment with Cur （20mol/L） combined with VCR （2 or 3 μg/mL） for 24 h, the expression level of MDR1 mRNA in Eca-IO9/VCR cells was significantly reduced （both P 〈 0.05）, and the expression levels of P-gp and MRP were significantly decreased as compared with VCR （2μg/mL） treatment group （all P 〈 0.05）. Conclusion： Cur can reverse multidrug resistance of esophageal cancer Eca-109/VCR cells and its mechanism may b

关 键 词：食管肿瘤 姜黄素 抗药性 肿瘤 多药耐药相关蛋白质类 

分 类 号：R915[医药卫生—微生物与生化药学]