| 张旭,程远方,张江霞,等.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[J].安徽医药,2020,24(5):860-864. |
| 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 |
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| DOI：10.3969/j.issn.1009?6469.2020.05.003 |
| 中文关键词: 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 |
| 英文关键词: Emodin Gemcitabine Pancreatic neoplasms Multidrug resistance?associated proteins P?glycoprotein Pancreatic cancer SW1990 cells Multi?drug resistance gene?1 miRNA?1271 |
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| 中文摘要: |
| 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( 40 μmol/L)、吉西他滨( 20 μmol/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。 |
| 英文摘要: |
| Objective To investigate the inhibitory effect of gemcitabine combined with emodin on the growth of pancreatic cancerSW1990 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(40 μmol/L)，gemcitabine(20 μmol/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 cancercells.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 combinedgroup 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 theemodin group(P＜0.05).The expression of E?cadhcrin protein in the combined group was significantly higher than that in othergroups.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 gemcitabine，and can inhibit EMT transformation of pancreatic cancer cells by increasing miRNA?1271. |
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