姜黄素联合吉西他滨对胰腺癌细胞体外增殖、凋亡及肿瘤干细胞表型特征的影响  

Synergistic Effect of Curcumin plus Gemcitabine Combination Therapy on the Proliferation,Apoptosis and Cancer Stem Cell Phenotype of Pancreatic Cancer Cells

作　　者：许琮[1] 夏超[1] 李德民[1] 常莹[1] 赵秋[1,2] 

机构地区：[1]华中科技大学同济医学院附属同济医院消化内科,武汉430030 [2]武汉大学中南医院消化内科,武汉430071

出　　处：《华中科技大学学报（医学版）》2015年第5期499-504,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金青年基金资助项目(No.81302112)

摘　　要：目的研究联合使用姜黄素及吉西他滨对胰腺癌细胞增殖、凋亡及肿瘤干细胞表型特征的影响,初步评价姜黄素治疗胰腺癌的临床应用前景。方法采用恶性程度、分化程度不同的胰腺癌细胞系panc03.27、Capan-2及PANC-1细胞,分为DMSO处理组、单纯吉西他滨处理组、单纯姜黄素处理组以及吉西他滨联合姜黄素处理组,采用CCK8(Cell Counting Kit-8)试剂盒测定细胞增殖力的改变;同时采用FITC Annexin V凋亡检测试剂盒分析不同处理组之间细胞凋亡率的差异,利用Western blot检测胰腺癌干性基因Notch1及Oct4的表达改变。结果 Panc03.27细胞中与单纯使用吉西他滨比较,联合使用姜黄素组细胞活力由(46.70±3.49)%下降为(35.53±1.84)%(P=0.047),细胞凋亡率由(5.01±0.75)%上升至(13.11±0.89)%(P<0.01),Notch1及Oct4表达明显下调(均P<0.01);Capan-2细胞中与单纯使用吉西他滨比较,联合使用姜黄素组细胞活力由(47.13±2.39)%下降至(5.36±0.25)%(P<0.01),细胞凋亡率由(13.02±1.79)%上升至(20.11±1.11)%(P<0.01),而Notch1及Oct4表达未见明显差异;PANC-1细胞中与单纯使用吉西他滨比联合使用姜黄素组细胞活力由(82.59±5.69)%下降至(7.33±0.25)%(P<0.01),细胞凋亡率由(6.77±2.03)%上升至(25.08±3.14)%(P<0.01),Notch1及Oct4表达明显下调(P<0.05)。结论姜黄素可协同吉西他滨抑制胰腺癌细胞的增殖、诱导细胞的凋亡及抑制肿瘤干细胞表型特征。Objective To investigate the effect of combination therapy with curcumin and gemcitabine on the proliferation,apoptosis and cancer stem cell phenotype of pancreatic cancer cells in order to preliminarily examine the application potential of curcumin to the treatment of pancreatic cancer.Methods Human pancreatic cancer cell lines of different malignancy and differentiation,panc 03.27,Capan-2 and PANC-1,were used in this study.They were divided into DMSO group,gemcitabine treatment group,curcumin treatment group and gemcitabine＋curcumin treatment group in terms of different treatments.Cell counting Kit-8 assay and flow cytometry were employed to detect the proliferation activity and apoptosis rate of these pancreatic cancer cells,respectively.The protein expression of genes associated with cancer stem cells（Notch 1 and Oct 4）was measured by Western blot.Results Comparison of the proliferation and apoptosis between the single gemcitabine group and the combination group found that,in panc03.27 cells,the cell viability was reduced from（46.70±3.49）%to（35.53±1.84）%（P=0.047）,the apoptosis rate was increased from（5.01±0.75）%to（13.11±0.89）%（P〈0.01）and the expression levels of Notch1 and Oct4were suppressed（P〈0.01）;in Capan-2cells,the cell viability was reduced from（47.13±2.39）% to（5.36±0.25）%（P〈0.01）,the apoptosis rate was increased from（13.02±1.79）% to（20.11±1.11）%（P〈0.01）,and the expression levels of Notch1 and Oct4were not significantly different;in PANC-1cells,the cell viability was reduced from（82.59±5.69）%to（7.33±0.25）%（P〈0.01）,the apoptosis rate was increased from（6.77±2.03）% to（25.08±3.14）%（P〈0.01）,and the expression levels of Notch1 and Oct4were suppressed（P〈0.05）.Conclusion Curcumin can synergistically inhibit the proliferation,promote the apoptosis of pancreatic cancer cells,and suppress the phenotype of cancer stem cells when used with gemcitabine.

关 键 词：胰腺癌 姜黄素 吉西他滨 联合用药 

分 类 号：R735.9[医药卫生—肿瘤]