帕纳替尼调控miR-92b-3p对胆管癌恶性生物学行为的影响  

Effects of panatinib regulation of miR-92b-3p on malignant biological behavior of cholangiocarcinoma

作　　者：邱实 杜杰 罗刚 林一煌 张子强 江帆 QIU Shi;DU Jie;LUO Gang;LIN Yi-huang;ZHANG Zi-qiang;JIANG Fan(Department of Gallstone Disease Center,Wuhan Puren Hospital,Wuhan 430080,Hubei Province,China;Department of Hepatobiliary and Pancreatic Surgery,Wuhan Puren Hospital,Wuhan 430080,Hubei Province,China)

机构地区：[1]武汉市普仁医院胆石病中心,湖北武汉430080 [2]武汉市普仁医院肝胆胰疝外科,湖北武汉430080

出　　处：《中国临床药理学杂志》2024年第19期2847-2852,共6页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究帕纳替尼对胆管癌(CCA)的影响及分子作用机制。方法将QBC939细胞分为对照组(不做任何处理)、低剂量组(0.1μmol·L^(-1)帕纳替尼处理)、中剂量组(0.5μmol·L^(-1)帕纳替尼处理)、高剂量组(1.0μmol·L^(-1)帕纳替尼处理)、高剂量+microRNA-92b-3组(1.0μmol·L^(-1)帕纳替尼处理后转染miR-92b-3p mimic)、高剂量+miR-92b-3p mimic+过表达同源结构域相互作用蛋白激酶3质粒(oe-HIPK3)组(1.0μmol·L^(-1)帕纳替尼处理后转染miR-92b-3p mimic和oe-HIPK3)、mimic-NC组(转染miR-92b-3p NC)、miR-92b-3p mimic组(转染miR-92b-3p mimic)。用细胞计数试剂盒8检测细胞的增殖情况,用Transwell实验法检测细胞迁移,用蛋白质印迹法检测蛋白相对表达水平。结果对照组、高剂量组、高剂量+miR-92b-3p mimic组、高剂量+miR-92b-3p mimic+oe-HIPK3组的细胞增殖率分别为(76.58±8.56)%、(61.85±7.77)%、(74.54±7.68)%和(58.63±6.87)%,细胞迁移数量分别为(185.32±20.14)、(132.33±18.99)、(168.23±19.85)和(138.66±15.95)个,磷酸化磷脂酰肌醇3-激酶(p-PI3K)/PI3K比值分别为1.00±0.23、0.68±0.09、0.91±0.18和0.60±0.08,磷酸化蛋白激酶B(p-AKT)/AKT比值分别为1.00±0.25、0.61±0.08、1.12±0.28和0.72±0.14;高剂量组的上述指标与对照组比较,高剂量+miR-92b-3p mimic组的上述指标与高剂量组比较,高剂量+miR-92b-3p mimic+oe-HIPK3组的上述指标与高剂量+miR-92b-3p mimic组比较,在统计学上差异均有统计学差异(均P<0.05)。结论帕纳替尼能有效抑制胆管癌的恶性生物学行为,可能与抑制miR-92b-3p水平,促进HIPK3介导的PI3K/AKT信号通路有关。Objective To study the effect of panatinib on cholangiocarcinoma(CCA)and its molecular mechanism.Methods QBC939 cells were divided into control group(no treatment),low dose group(0.1μmol·L^(-1)panatinib treatment),medium dose group(0.5μmol·L^(-1)panatinib treatment),high dose group(1.0μmol·L^(-1)panatinib treatment)and high dose+microRNA-92b-3 group(after treatment with 1.0μmol·L^(-1)panatinib transfected miR-92b-3p mimic),high-dose+miR-92b-3p mimic+overexpressed homologous domain interacting protein kinase 3 plasmid(oe-HIPK3)group(after treatment with 1.0μmol·L^(-1)panatinib,miR-92b-3p mimic and oe-HIPK3),mimic-NC group(transfected miR-92b-3p NC),and miR-2b-3p mimic group(transfected miR-92b-3p mimic)were transfected.Cell proliferation was detected by cell counting kit 8(CCK-8);cell migration was detected by Transwell,the relative expression level of protein was detected by Western blot.Results Cell proliferation rates of control group,high-dose group,high-dose+miR-92b-3p mimic group,and high-dose+miR-92b-3p mimic group mimic+oe-HIPK3 group were(76.58±8.56)%,(61.85±7.77)%,(74.54±7,68)%and(58.63±6.87)%Respectively;the number of cells migrated were 185.32±20.14,132.33±18.99,168.23±19.85 and 138.66±15.95,respectively;phosphorylated phosphatidyl inositide 3-kinase(p-PI3K)/PI3K ratios were 1.00±0.23,0.68±0.09,0.91±0.18 and 0.60±0.08,respectively;phosphorylated protein kinase B(p-AKT)/AKT ratios were 1.00±0.25,0,61±0.08,1.12±0,28 and 0.72±0.14,respectively.The above indexes were compared with those of the control group in the high-dose group,and those of the high-dose+miR-92b-3p mimic group in the high-dose+miR-92b-3p mimic group in the oe-HIPK3 group.There were statistically significant differences(all P<0.05).Conclusion Panatinib can effectively inhibit the evil biological behavior of cholangiocarcinoma,which may be related to inhibiting the level of miR-92b-3p and promoting HIPK3-mediated PI3K/AKT signaling pathway.

关 键 词：帕纳替尼 非编码微小RNA-92b-3p 胆管癌 同源结构域相互作用蛋白激酶3 磷脂酰肌醇3-激酶/蛋白激酶B信号通路 

分 类 号：R979.1[医药卫生—药品]