miR-425-5p靶向成纤维细胞生长因子9对卵巢癌细胞的作用  

Effects of miR-425-5p targeting fibroblast growth factor 9 on ovarian cancer cells

作　　者：蔡怡园[1] 袁泉 张雅秋 钟金妍[1] CAI Yi-yuan;YUAN Quan;ZHANG Ya-qiu;ZHONG Jin-yan(Department of Gynaecology,Qingdao Hiser Hospital Affiliated of Qingdao University(Qingdao Traditional Chinese Medicine Hospital),Qingdao 266033,Shandong Province,China;Department of Pharmacy,Qingdao Hiser Hospital Affiliated of Qingdao University(Qingdao Traditional Chinese Medicine Hospital),Qingdao 266033,Shandong Province,China)

机构地区：[1]青岛大学附属青岛市海慈医院(青岛市中医医院)妇科,山东青岛266033 [2]青岛大学附属青岛市海慈医院(青岛市中医医院)药剂科,山东青岛266033

出　　处：《中国临床药理学杂志》2025年第4期487-491,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究微小RNA-425-5p(miR-425-5p)靶向成纤维细胞生长因子9(FGF9)对卵巢癌细胞的增殖、葡萄糖代谢和奥拉帕利耐药性的影响机制。方法将人卵巢癌细胞株SKOV3分为对照组(正常培养)、NC inhibitor组(转染空载体miR-NC)、miR-425-5p inhibitor组(转染miR-425-5p抑制剂)、si-NC组(在miR-425-5p inhibitor组的基础上转染si-NC)、si-FGF9组(在miR-425-5p inhibitor组的基础上转染si-FGF9)。用实时定量聚合酶链反应检测miR-425-5p和FGF9 mRNA在细胞中的表达水平,用5-乙炔基-2'-脱氧尿苷(EdU)实验检测细胞增殖率,用乳酸代谢和葡萄糖检测试剂盒检测各组细胞乳酸生成量和葡萄糖吸收量,用细胞计数试剂盒-8实验检测各组细胞的存活率,用蛋白质印迹法检测各组细胞信号传导转录激活因子3/沉默调节蛋白3(STAT3/SITR3)信号通路相关蛋白的表达水平。结果NC inhibitor组、miR-425-5p inhibitor组、si-NC组和si-FGF9组的增殖率分别为(84.11±14.76)%、(36.12±6.95)%、(34.32±6.62)%和(77.37±12.83)%,相对乳酸生成量分别为1.02±0.13、0.71±0.09、0.74±0.09和0.89±0.10,相对葡萄糖吸收值分别为0.99±0.14、0.68±0.08、0.70±0.09和0.91±0.11,在40μmol·L^(-1)奥拉帕利处理下的存活率分别为(59.86±9.55)%、(41.08±7.72)%、(40.25±7.02)%和(55.71±7.68)%,STAT3蛋白相对表达水平分别为1.01±0.17、0.68±0.10、0.66±0.09和0.88±0.12,SITR3蛋白相对表达水平分别为0.98±0.17、1.84±0.28、1.85±0.29和1.23±0.20。miR-425-5p inhibitor组的上述指标与NC inhibitor组比较,si-FGF9组的上述指标与si-NC组比较,在统计学上差异均有统计学意义(P<0.01,P<0.001)。结论沉默miR-425-5p会抑制卵巢癌细胞的增殖和葡萄糖代谢,降低细胞对奥拉帕利的耐药性,可能是通过上调FGF9水平,进而抑制STAT3/SIRT3信号通路来实现的。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-425-5p 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 40μmol·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 gr

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 

分 类 号：R97[医药卫生—药品]