microRNA-10b与胰腺癌吉西他滨耐药的相关性及机制研
究
顾燊;邵欣宇;邹晓平
【期刊名称】《南京医科大学学报（自然科学版）》 【年(卷),期】2017(037)007
【摘要】目的:探讨microRNA-10b(miR-10b)与胰腺癌细胞吉西他滨(gemcitabine,GEM)化疗耐药的相关性及可能机制.方法:RT-qPCR检测吉西他滨相对耐药的胰腺癌细胞株PANC-1及吉西他滨相对敏感的CFPAC-1中miR-10b的表达情况;用不同浓度的吉西他滨作用于上述细胞,RT-qPCR检测二者miR-10b的表达变化;CFPAC-1细胞转染miR-10b mimics上调miR-10b表达量,CCK-8法及流式细胞仪检测细胞对吉西他滨药物敏感性的变化,Western blot检测抗凋亡相关蛋白(如PI3K、p-Akt、Bcl-2、Survivin)的表达,RT-qPCR检测PTEN基因的表达变化.结果:PANC-1细胞中miR-10b的表达显著高于CFPAC-1细胞,且上述两种细胞中miR-10b的表达量与吉西他滨呈浓度梯度依赖;高表达miR-10b后CFPAC-1细胞对吉西他滨的敏感性下降,PI3K、p-Akt、Bcl-2、Survivin蛋白的表达升高,PTEN mRNA的表达水平降低.结论:miR-10b可能通过负性调控PTEN的表达水平,从而增加PI3K、p-Akt、Bcl-2、Survivin蛋白的表达,减少凋亡来降低CFPAC-1对吉西他滨的敏感性,最终导致胰腺癌细胞对吉西他滨化疗耐受.%Objectives:To reveal the relationship between microRNA-10b and gemcitabine (GEM) resistance of pancreatic cancer and its possible mechanism.Methods:The expression of microRNA-10b in PANC-1 cells (which are relatively resistant to GEM) and CFPAC-1 cells
(which are relatively sensitive to GEM) were detected by RT-qPCR.PANC-1 and CFPAC-1 cells were treated with different doses of GEM,and then the cells were harvested.The expression of microRNA-10b was detected by RT-qPCR.CCK-8 assay and flow cytometry were performed to evaluate the drug sensitivity of CFPAC-1 cells,which were transfected with microRNA-10b mimics to GEM.The protein expressions of PI3K,p-Akt,Bcl-2 and Survivin in CFPAC-1 cells transfected with microRNA-10b mimics or negative control were demonstrated using Western blotting assay.The gene expressions of PTEN in CFPAC-1 cells transfected with microRNA-10b mimics or negative control were detected by RT-qPCR.Results:PANC-1 cells showed significantly increased expression of microRNA-10b as compared to CFPAC-1 cells.The expression of microRNA-10b both in PANC-1 and CFPAC-1 cells increased with the rising of GEM concentration.The sensitivity of CFPAC-1 cells to GEM decreased when microRNA-10b was overexpressed and the expressions of PI3K,p-Akt,Bcl-2,and Survivin were much higher than their control groups.The expression of PTEN mRNA decreased as microRNA-10b increased.Conclusions:MicroRNA-10b might negatively regulate the gene expression of PTEN,which increases the protein expressions of PI3K,p-Akt,Bcl-2 and Survivin,thus reduces the sensitivity of CFPAC-1 cells to GEM,and as a result,pancreatic cancer cells become resistant to GEM.
【总页数】6页(830-835)
【关键词】microRNA-10b;胰腺癌;吉西他滨;化疗耐药 【作者】顾燊;邵欣宇;邹晓平
【作者单位】南京医科大学附属鼓楼临床医学院,江苏南京210008;启东市人民医院消化内科,江苏启东226200;南京医科大学附属鼓楼临床医学院,江苏南京210008;南京大学医学院附属鼓楼医院消化科,江苏南京210008 【正文语种】中文 【中图分类】R735.9 【文献来源】
https://www.zhangqiaokeyan.com/academic-journal-cn_journal-nanjing-medical-university-natural-sciences_thesis/0201245363647.html 【相关文献】
1.Aurora-A在胰腺癌的表达及与吉西他滨耐药的相关性研究 [J], 何永礼; 王欣; 施福田; 严秋亮; 朱锦辉
2.胰腺癌患者循环microRNA及吉西他滨耐药的胰腺癌患者特异性microRNA表达谱分析 [J], 王书艺; 周翡; 王理伟
3.dCK基因A9846G单核苷酸多态性与胰腺癌吉西他滨化疗预后的相关性 [J], 陈果[1]; 熊俊杰[2]; 杜玲[3]; 刘显军[1]; 王清卿[1]
4.胰腺癌RRM1、hENT1蛋白表达及其与吉西他滨化疗效果的相关性 [J], 徐媛; 李艺; 徐蔚蔚
5.RRMl、hENT1的表达与胰腺癌吉西他滨化疗疗效相关性研究进展 [J], 王天
microRNA-10b与胰腺癌吉西他滨耐药的相关性及机制研究
