miR-320e促进胰腺癌细胞系耐药

miR-320e promotes drug resistance of pancreatic cancer cell line

目的研究miR-320e在胰腺癌耐药中的作用及其机制。方法用定量PCR的方法确定miR-320e在胰腺癌耐药细胞系中的表达,进而通过在胰腺癌细胞中过表达miR-320e,检测细胞对5-FU化疗药物敏感性、细胞增殖的影响。同时通过报告基因实验及Western blot法确定miR-320e的靶基因。结果在胰腺癌耐药细胞系(PATU8988/5-FU)中miR-320e表达显著上升(P<0.01)。在胰腺癌细胞PATU8988和PANC-1中过表达miR-320e后,细胞对5-FU化疗药物出现耐受,IC_(50)显著上升(P<0.01),细胞增殖速度加快(P<0.01)。PDCD4是miR-320e的直接靶基因,miR-320e的过表达显著降低了PDCD4蛋白水平。结论 miR-320e的高表达可显著促发胰腺癌细胞化疗耐药,可作为胰腺癌耐药检测的分子标志及新的治疗靶点。

Objective To explore the function and mechanism of miR-320e in drug-resistance of pancreatic cancer.Methods Q-PCR was used to detect the expression of miR-320e in 5-FU resistant pancreatic cancer cells. miR-320e was overexpressed in PATU8988 and PANC-1 pancreatic cancer cells and then drug sensitivity and cell proliferation were checked. In addition,luciferase reporter assay and Western blot were used to identify the target of miR-320e. Results miR-320e was significantly up-regulated in the 5-FU resistant PATU8988 cells. The overexpression of miR-320e in pancreatic cancer cells significantly promoted cell survival when treated with 5-FU,and also advanced cell proliferation rate. miR-320e also decreased the protein level of PDCD4 and PDCD4 3＇ UTR dependent luciferase activity. miR-320e promoted drug-resistance by targeting PDCD4. Conclusions miR-320e can induce 5-FU resistance of pancreatic cancer cells and might be a potential biomarker of drug-resistance and a chemotherapy target for pancreatic cancer.