大黄素联合吉西他滨抑制胰腺癌细胞系PANC-1细胞增殖能力的研究  

Inhibitory Effect of Emodin and Gemcitabine on Proliferation of Pancreatic Cancer Cell Line PANC-1

作　　者：王婧[1] 赵磊[1] 车娟娟[1] 李卉惠[1] 庞歆桥 吴军[1] 马妮娜[1] 

机构地区：[1]首都医科大学附属北京友谊医院肿瘤科,北京100050

出　　处：《肿瘤预防与治疗》2016年第3期139-143,共5页Journal of Cancer Control And Treatment

基　　金：国家自然科学基金资助(81000187);北京市医院管理局"青苗"计划专项经费资助(QML20150107);北京市中医药科技发展资金项目资助(QN2015-08);首都卫生发展科研专项基金资助(2016);首都医科大学基础-临床合作课题资助项目(14JL31);首都医科大学附属北京友谊医院院启动基金资助(yyqdkt2014-10)

摘　　要：目的:验证大黄素联合吉西他滨(gemcitabine,GEM)抑制胰腺癌细胞系PANC-1细胞增殖的作用,探讨大黄素促PANC-1细胞凋亡的抗肿瘤作用机制。方法:MTT方法检测大黄素单药以及与吉西他滨联合应用对PANC-1细胞增殖能力的影响。ELISA方法测定细胞上清IL-6水平。RT-PCR方法检测大黄素处理后PANC-1细胞内侵袭相关基因MMP-9的表达情况。Western blot方法分别检测大黄素以及吉西他滨处理PANC-1后凋亡相关蛋白Bax和Bcl-2的表达水平。结果:MTT检测结果显示,加药处理细胞72h后,大黄素组(40μmol/l)PANC-1细胞抑制率为31%,GEM组(20μmol/l)的抑制率为35%,联合用药组的抑制率为49%,与对照组相比差异有统计学意义(P<0.05)。IL-6浓度大黄素组为(22.41±2.27)ng/ml,联合用药组为(15.44±3.91)ng/ml。实验组均显著低于对照组,差异有统计学意义(P<0.05)。大黄素组、联合用药组MMP-9 mRNA表达水平显著低于对照组,GEM组较对照组相比差异无统计学意义(P>0.05)。大黄素组、GEM组、联合用药组Bax表达水平上调,但Bcl-2差异无统计学意义。大黄素组、GEM组、联合用药组的Bax/Bcl-2分别为2.71±0.25,4.73±0.17,5.72±0.36,均显著高于对照组1.14±0.15,结论:体外研究结果显示大黄素能够抑制肿瘤PANC-1细胞增殖,具有促细胞凋亡的作用,与吉西他滨联合应用具有协同效应。Objective： To investigate the antitumor mechanisms of emodin with gemcitabine in the pancreatic cancer cell line PANC-1 by proliferation,migration and invasion. Methods： The cell proliferation of PANC-1 intervened by emodin with or without gemcitabine was detected by 4-methyl-teerazolium（ MTT）. IL-6 was measured by ELISA from cellular supernatant. The expression of the gene MMP-9 was detected by RT-PCR. Bax and Bcl-2 protein were detected by western blot. Results： The PANC-1 cell inhibition rate was 31% in Emodin group（ 40μmol / l）,35% in the GEM group（ 20μmol/l）,and 49% in the combination group. Statistically significant differences were observed between these three groups with the control group（ P〈0. 05）. IL-6 concentration of emodin group and combination group was（ 22. 41 ± 2. 27）ng / ml and（ 15. 44 ± 3. 91） ng / ml,respectively. IL-6 concentration of the experimental groups were significantly lower than that of the control group with statistically significant difference（ P〈0. 05）. MMP-9 mRNA expression level of emodin group and combination group were significantly lower than that of the control group. Bax / Bcl-2 of emodin group,GEM group and combination group were（ 2. 71 ± 0. 25）,（ 4. 73 ± 0. 17）,and（ 5. 72 ± 0. 36） respectively,which were significantly higher than that of control group（ 1. 14 ±0. 15）. Conclusion： In vitro studies show that emodin can inhibit the proliferation and stimulate the apoptosis of pancreatic cancer cell line PANC-1,furthermore,when comined with gemcitabine,emodin has stronger antitumor effect.

关 键 词：大黄素 胰腺癌 凋亡 

分 类 号：R735.9[医药卫生—肿瘤] R730-3[医药卫生—临床医学]