酮咯酸通过胰岛素样生长因子2信号通路抑制卵巢癌的生长和转移  

Ketorolac inhibits ovarian cancer growth and metastasis via IGF2 signaling pathway

作　　者：冯艳坤 陈治军 FENG Yankun;CHEN Zhijun(Department of Anesthesiology,Wuhan No.1 Hospital,Wuhan,Hubei 430022,China)

机构地区：[1]武汉市第一医院麻醉科,湖北武汉430022

出　　处：《安徽医药》2023年第1期190-194,I0009,共6页Anhui Medical and Pharmaceutical Journal

基　　金：国家自然科学基金(81460177)。

摘　　要：目的探讨酮咯酸对卵巢癌生长、转移影响及机制。方法实验于2019年8月至2020年3月进行。细胞计数试剂盒(CCK-8)法检测不同剂量(0.10 g/L、0.50 g/L、1.00 g/L、1.50 g/L)酮咯酸对人卵巢癌细胞SKOV3的抑制率,筛选酮咯酸的最佳作用浓度。SKOV3细胞分为NC组、酮咯酸组、DMSO组、Linsitinib组、酮咯酸+pcDNA 3.1组和酮咯酸+pcDNA 3.1-IGF2组,TraNC‐well法检测各组细胞迁移和侵袭,蛋白质印迹法(Western blotting)法检测各组细胞中胰岛素样生长因子2(IGF2)、胰岛素样生长因子1受体(IGF1R)的蛋白表达。裸鼠分为NC组和酮咯酸组,每组10只,观察酮咯酸对肿瘤生长及肿瘤组织中IGF2、IGF1R的蛋白表达的影响。结果与NC组相比,不同剂量(0.10、0.50、1.00、1.50 g/L)酮咯酸组细胞抑制率升高[(6.99±0.06)%、(23.31±2.11)%、(51.39±6.91)%、(76.14±4.36)%比(0.02±0.00)%,P<0.05],选择1.0 g/L酮咯酸为最佳浓度。与NC组相比,酮咯酸组细胞迁移数[(54±5)个比(103±9)个]和侵袭数[(41±4)个比(76±6)个]及细胞中IGF2(0.31±0.03比1.01±0.06)和IGF1R蛋白(0.26±0.02比0.99±0.08)表达均显著降低(均P<0.05)。与NC组或DMSO组相比,Linsitinib组细胞迁移数[(63±6)个比(98±9)个、(99±7)个]和侵袭数[(51±5)个比(73±6)个、(75±6)个]及细胞中IGF2(0.28±0.02比0.98±0.05、1.00±0.07)和IGF1R(0.29±0.02比0.99±0.06、1.02±0.08)蛋白表达均显著降低(均P<0.05)。与酮咯酸组或酮咯酸+pcDNA 3.1组相比,酮咯酸+pcDNA 3.1-IGF2组细胞迁移数[(87±7)个比(52±5)个、(53±5)个]和侵袭数[(75±6)个比(44±4)个、(42±4)个]及细胞中IGF2(1.28±0.13比0.31±0.03、0.33±0.04)和IGF1R(1.19±0.12比0.26±0.02、0.27±0.03)蛋白表达均显著升高(均P<0.05)。与NC组相比,酮咯酸组裸鼠肿瘤的质量[(0.53±0.05)g比(1.01±0.07)g]和体积[(0.55±0.05)cm^(3)比(1.00±0.04)cm^(3)]均显著降低(P<0.05),肿瘤组织中IGF2(0.46±0.04比0.99±0.08)和IGF1R(0.52±0.05比0.97±0.09)蛋白表达均显著降低Objective To investigate the effect of ketorolac on the growth and metastasis of ovarian cancer and its mechanism.Meth⁃ods Experiments were conducted from August 2019 to March 2020.Cell counting kit(CCK-8)method was used to detect the inhibi‐tion rates of ketorolac(0.10 g/L,0.50 g/L,1.00 g/L,1.50 g/L)on human ovarian cancer cell line SKOV3.The optimal concentration of ketorolac was sorted out.Patients were assigned into NC group,ketorolac group,DMSO group,Linsitinib group,ketorolac+pcDNA 3.1 group and ketorolac+pcDNA3.1-IGF2 group.Cell migration and invasion were detected by TraNCwell,the protein expressions of insu‐lin-like growth factor 2(IGF2)and insulin-like growth factor 1 receptor(IGF1R)were detected by western blotting.Nude mice were as‐signed into NC group and ketorolac group,with 10 in each group.Observation was made of the effect of ketorolac on tumor growth and protein expressions of IGF2 and IGF1R in tumor tissue.Results Compared with the NC group,the cell inhibition rates of ketorolac groups at different doses(0.10 g/L,0.50 g/L,1.00 g/L,1.50 g/L)increased[(6.99±0.06)%,(23.31±2.11)%,(51.39±6.91)%,(76.14±4.36)%vs.(0.02±0.00)%,P<0.05],and 1.00 g/L of ketorolac was selected as the best concentration.Compared with the NC group,the number of cell migration[(54±5)vs.(103±9)],the number of invasion[(41±4)vs.(76±6)]and the protein expressions of IGF2[(0.31±0.03)vs.(1.01±0.06)]and IGF1R[(0.26±0.02)vs.(0.99±0.08)]in the ketorolac groups were significantly reduced(all P<0.05).Com‐pared with the NC group or the DMSO group,the number of cell migration[(63±6)vs.(98±9),(99±7)],the number of invasion[(51±5)vs.(73±5),(75±6)]and the protein expressions of IGF2[(0.28±0.02)vs.(0.98±0.05),(1.00±0.07)]and IGF1R[(0.29±0.02)vs.(0.99±0.06),(1.02±0.08)]in the Linsitinib group were significantly reduced(all P<0.05).Compared with the ketorolac group or the ketorolac+pcDNA 3.1 group,the number of cell migration[(87±7)vs.(52±5),(53±5)],the number of cell invasion[(75±6)vs.(44±4),(42±4)]and

关 键 词：酮咯酸 IGF2信号通路 卵巢肿瘤 迁移 侵袭 免疫印迹法 TraNCwell 小鼠 近交BALB C 

分 类 号：R737.31[医药卫生—肿瘤]