摘要
Abstract
Objective To investigate the effects of microRNA-425-5p(miR-425-5p)targeting fibroblast growth factor 9(FGF9)on the proliferation,glucose metabolism and olaparib resistance of ovarian cancer cells.Methods Human ovarian cancer cell line SKOV3 were divided into control group(normal culture),NC inhibitor group(transfected empty vector miR-NC),miR-425-5p inhibitor group(transfected miR-425-5 p inhibitor),si-NC group(transfected si-NC on the basis of miR-425-5p inhibitor group),si-FGF9 group(transfected si-FGF9 on the basis of miR-425-5p inhibitor group).Quantitative real time polymerase chain reaction was used to detect the expression levels of miR-425-5p and FGF9 in cells.The cell proliferation rate was detected by 5-ethynyl-2'-deoxyuridine(EdU)assay.Lactic acid production and glucose absorption were measured by lactic acid metabolism and glucose detection kit.The survival rate of cells in each group was detected by cell counting kit-8 assay.Western blot was used to detect signal transducer and activator of transcription 3/sirtuin 3(STAT3/SITR3)signaling pathway related protein expression levels in each group.Results The proliferation rate were(84.11±14.76)%,(36.12±6.95)%,(34.32±6.62)%and(77.37±12.83)%in the NC inhibitor group,miR-425-5p inhibitor group,si-NC group and si-FGF9 group,respectively;the relative lactic acid production were 1.02±0.13,0.71±0.09,0.74±0.09 and 0.89±0.10,respectively;the relative glucose absorption values were 0.99±0.14,0.68±0.08,0.70±0.09 and 0.91±0.11,respectively;the survival rates under 40 μmol·L-1 olaparib were(59.86±9.55)%,(41.08±7.72)%,(40.25±7.02)%and(55.71±7.68)%,respectively;the relative expression levels of STAT3 protein were 1.01±0.17,0.68±0.10,0.66±0.09 and 0.88±0.12,respectively;the relative expression levels of SITR3 protein were 0.98±0.17,1.84±0.28,1.85±0.29 and 1.23±0.20,respectively.The above indexes of miR-425-5p inhibitor group were compared with those of NC inhibitor group,and those of si-FGF9 group were compared with those of si-NC inhibitor group,and the differences were statistically significant(P<0.01,P<0.001).Conclusion Silting miR-425-5p can inhibit the proliferation and glucose metabolism of ovarian cancer cells,and reduce the resistance of cells to olaparib,which may be achieved by up-regulating FGF9 level and inhibiting STAT3/SIRT3 signaling pathway.关键词
奥拉帕利/微小RNA-425-5p/卵巢癌/成纤维细胞生长因子9/信号传导转录激活因子3/沉默调节蛋白3/葡萄糖代谢Key words
olaparib/microRNA-425-5p/ovarian cancer/fibroblast growth factor 9/signal transducer and activator of transcription 3/sirtuin 3/glucose metabolism分类
医药卫生