吉西他滨联合大黄素对胰腺癌SW1990细胞多耐药基因 1、miRNA 1271及上皮-间充质细胞转化的影响  

Effects of gemcitabine combined with emodin on MDR 1,miRNA 1271 and EMT in pancreatic cancer SW1990 cells

作　　者：张旭 程远方[2] 张江霞 宋沛然 张静 ZHANG Xu;CHENG Yuanfang;ZHANG Jiangxia;SONG Peiran;ZHANG Jing(Department of Pharmacy,Nanshi Hospital,Nanyang,Henan 473000,China;Department of Pharmacy,Henan Cancer Hospital,Zhengzhou,Henan 450008,China)

机构地区：[1]南石医院药学部,河南南阳473000 [2]河南省肿瘤医院药学部,河南郑州450008

出　　处：《安徽医药》2020年第5期860-864,共5页Anhui Medical and Pharmaceutical Journal

摘　　要：目的探究吉西他滨联合大黄素对胰腺癌SW1990细胞生长的抑制作用及对多耐药基因 1(MDR 1)、miRNA 1271和上皮-间充质细胞转化(EMT)的影响。方法将胰腺癌SW1990细胞分为大黄素组(40μmol/L)、吉西他滨(20μmol/L)、吉西他滨联合大黄素组及对照组(生理盐水),流式细胞仪检测细胞凋亡,MTT法检测细胞增殖,Transwell小室模型检测胰腺癌细胞侵袭能力,实时荧光定量聚合酶链反应(qRT PCR)检测MDR 1、miRNA 1271及EMT相关标志物(TWIST1、ZEB1、E cadhcrin)mRNA表达,流式细胞仪检测MDR 1编码的P糖蛋白(P gp)阳性率,蛋白质免疫印迹法检测肿瘤组织凋亡相关蛋白[B淋巴细胞瘤2(Bcl 2)及其相关X蛋白(Bax)、胱天蛋白酶3(Caspase 3)及Survivin]及EMT相关标志物蛋白含量。结果联合组可显著抑制胰腺癌SW1990细胞增殖和侵袭,SW1990细胞凋亡率显著更高,与其他三组比较差异有统计学意义(P<0.05)。联合组MDR 1 mRNA显著降低,miRNA 1271及E cadhcrin mRNA显著升高,且与其他组比较差异有统计学意义(P<0.05),各组TWIST1、ZEB1 mRNA水平比较差异无统计学意义(P>0.05)。联合组可以显著抑制Bcl 2、Caspase 3及Survivin表达,上调Bax表达,降低Bcl 2、Bax比值,其效果明显高于吉西他滨组和大黄素组(P<0.05)。联合组E cadhcrin蛋白表达显著高于其他组,P gp、TWIST1、ZEB1蛋白表达显著低于其他组(P<0.05)。结论大黄素能够下调MDR 1降低胰腺癌细胞对吉西他滨耐药性,并能通过提高miRNA 1271抑制胰腺癌细胞EMT转化。Objective To investigate the inhibitory effect of gemcitabine combined with emodin on the growth of pancreatic cancer SW1990 cells and the transformation of multidrug resistance gene 1(MDR 1),miRNA 1271 and epithelial mesenchymal cells(The transformation of cpithclial mescnchymal,EMT).Methods Pancreatic cancer SW1990 cells were divided into the emodin group(40μmol/L),gemcitabine(20μmol/L),gemcitabine plus emodin group and the control group(normal saline).Apoptosis was detected by flow cytometry.Proliferation,Transwell chamber model was used to detect the invasion ability of pancreatic cancer cells.qRT PCR was used to detect mRNA expression of MDR 1,miRNA 1271 and EMT related markers(TWIST1,ZEB1,E cadh crin),P gp positive rate and MDR 1 coding was detected by flow cytometry.Western blot were adopted to detect tumor tissue apop tosis related proteins[B lymphocyte tumor 2(Bcl 2)and its related X protein(Bax),caspase 3(Caspase 3)And Survivin]and EMT related marker protein content.Results The proliferation and invasion of pancreatic cancer SW1990 cells in the combined group were significantly inhibited.The apoptosis rate of SW1990 cells was significantly higher than that of the other three groups(P<0.05).MDR 1 mRNA was significantly decreased in the combined group,and miRNA 1271 and E cadhcrin mRNA were signif icantly increased(P<0.05).There was no significant difference in TWIST1 and ZEB1 mRNA levels between the two groups(P>0.05).The expression of Bcl 2,Caspase 3 and Survivin,up regulate the expression of Bax,and decrease the ratio of Bcl 2 and Bax were significantly inhibited in the combination group.The effect was significantly higher than that of the gemcitabine group and the emodin group(P<0.05).The expression of E cadhcrin protein in the combined group was significantly higher than that in other groups.The expression of P gp,TWIST1 and ZEB1 protein was significantly lower than that in other groups(P<0.05).Conclu sion Emodin can down regulate MDR 1 and reduce the resistance of pancreatic cancer cells to gemcit

关 键 词：大黄素 吉西他滨 胰腺肿瘤 多药耐药相关蛋白质类 P糖蛋白 胰腺癌SW1990细胞 多耐药基因 1 微小RNA 1271 

分 类 号：R735.9[医药卫生—肿瘤]