microRNA-10b与胰腺癌吉西他滨耐药的相关性及机制研究

发布时间：2018-07-03 16:07

本文选题：microRNA-b + 胰腺癌　；参考：《南京医科大学学报(自然科学版)》2017年07期

【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。
[Abstract]:Aim: to investigate the relationship between microRNA-10b (miR-10b) and chemotherapeutic resistance of pancreatic cancer cell gemcitabine gem and its possible mechanism. Methods the expression of miR-10b in the relatively resistant pancreatic cancer cell line PANC-1 and the relatively sensitive CFPAC-1 was detected by RT-qPCR. Expression of miR-10b in the above cells treated with different concentrations of gemcitabine was detected by RT-qPCR. The expression of miR-10b mimics was up-regulated by CFPAC-1 cells. CCK-8 assay and flow cytometry were used to detect the sensitivity of the cells to gemcitabine. Western blot was used to detect the expression of miR-10b in CFPAC-1 cells. The expression of anti-apoptosis-related proteins (such as PI3KUp-AktC2Bcl-2survivin) was detected by RT-qPCR to detect the expression of PTEN gene. Results the expression of miR-10b in the cell line was significantly higher than that in the CFPAC-1 cell line, and the expression of miR-10b in the two cells was in a concentration-dependent manner. After overexpression of miR-10b, the sensitivity of CFPAC-1 cells to gemcitabine was decreased. Conclusion the expression of PTEN may be negatively regulated by 1: miR-10b, which may increase the expression of PI3KP- Aktnbcl-2survivin protein, reduce apoptosis and decrease the sensitivity of CFPAC-1 to gemcitabine, leading to the chemotherapeutic tolerance of pancreatic cancer cells to gemcitabine.
【作者单位】：南京医科大学附属鼓楼临床医学院;启东市人民医院消化内科;南京大学医学院附属鼓楼医院消化科;
【基金】：[基金项目]江苏省医学领军人才与创新团队(LJ201104)
【分类号】：R735.9

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