银杏素调节Nrf2、SLC7A11、GPX4信号通路对卵巢癌细胞及铁死亡的影响  

Effects of ginkgo biloba regulating nuclear factor E2 related factor 2/non glycosylated xCT/glutathione peroxidase 4 signaling pathway on the proliferation,apoptosis,and iron death of ovarian cancer cells

作　　者：芮玲 王文静 倪海莱[2] 侯兵[2] 张海燕[2] RUI Ling;WANG Wenjing;NI Hailai;HOU Bing;ZHANG Haiyan(Liyang People's Hospital,Jiangsu Province,213300;Shanghai Changhai Hospital)

机构地区：[1]江苏省溧阳市人民医院,213300 [2]上海长海医院

出　　处：《中国计划生育学杂志》2022年第12期2677-2682,共6页Chinese Journal of Family Planning

摘　　要：目的:探讨银杏素调节核因子E_(2)相关因子2(Nrf2)、非糖基化的xCT(SLC7A11)、谷胱甘肽过氧化物酶4(GPX4)信号通路对卵巢癌(OC)细胞增殖、凋亡和铁死亡的影响。方法:选取对数生长期SKOV3细胞,设置对照组、Nrf2激活剂-莱菔硫烷(SFN,20μmol SFN)组、银杏素低浓度组(2.5μM)、中浓度组(5μM)、高浓度(10μM)组、银杏素高浓度+SFN(10μM银杏素+20μmol SFN)组,对照组无需处理,其余各组按照相应药物浓度进行处理。MTT法检测各组SKOV3细胞增殖率;Western blot检测各组SKOV3细胞中Nrf2、SLC7A11、GPX4蛋白表达水平;qRT-PCR检测各组SKOV3细胞铁死亡影响因子SLC7A11、GPX4 mRNA表达水平;流式细胞仪检测各组SKOV3细胞凋亡率;qRT-PCR检测各组SKOV3细胞铁死亡影响因子SLC7A11、GPX4 mRNA表达水平;试剂盒检测各组SKOV3细胞铁水平变化;Western blot检测各组SKOV3细胞中Nrf2、SLC7A11、GPX4蛋白表达水平。结果:与对照组相比,SFN组增殖率(124.71±12.49)%、Nrf2(1.15±0.12)、SLC7A11(1.58±0.16)、GPX4(1.08±0.11)表达均升高,凋亡率(4.01±0.41)%、铁水平(24.73±2.48)下降(P<0.05),而银杏素低、中、高浓度组增殖率(74.22±7.43、51.03±5.11、35.23±3.53)%、Nrf2(0.62±0.07、0.41±0.05、0.18±0.02)、SLC7A11(0.56±0.06、0.37±0.04、0.16±0.02)、GPX4(0.61±0.07、0.43±0.05、0.21±0.03)表达均下降,凋亡率(14.55±1.46、28.17±2.82、42.01±4.21)%、铁水平(48.99±4.91、60.83±6.10、77.87±7.79)依次增加(均P<0.05);与银杏素高浓度+SFN组增殖率(65.09±6.51)%、Nrf2(0.48±0.05)、SLC7A11(0.46±0.05)、GPX4(0.55±0.06)表达相比,银杏素高浓度组增殖率、Nrf2、SLC7A11、GPX4表达及SFN组均有差异(均P<0.05)。结论:银杏素可以抑制OC细胞系SKOV3细胞的增殖,诱导其凋亡及铁死亡,可能与抑制Nrf2/SLC7A11/GPX4信号通路有关。Objective:To investigate the influence of ginkgo biloba regulating nuclear factor E_(2)related factor 2(Nrf2)/non glycosylated xCT(SLC7A11)/glutathione peroxidase 4(GPX4)on the proliferation,apoptosis,and iron death of ovarian cancer(OC)cells.Methods:SKOV3 cells in logarithmic growth phase were selected in study group and in control group.The SKOV3 cells in the study group were divided in group A(cells with the treatment of Nrf2 activator sulforaphane(SFN)of 20μmol),and group B1(cells with the treatment of low-concentration ginkgetin of 2.5μM),group B2(cells with the treatment of medium:concentration ginkgetinof 5μM),group B3(cells with the treatment of high-concentration ginkgetin of 10μM),group C(cells with the treatment of high-concentration ginkgetin of 10μM combined with SFN of 20μmol).And the cells in the control group did not given treatment.The proliferation rate of SKOV3 cells in each group was detected by MTT method.The protein expression levels of Nrf2,SLC7A11,and GPX4 in SKOV3 cells in these groups were detected by Western blot.The mRNA expression levels of iron death factors SLC7A11 and GPX4 in SKOV3 cells were detected by qRT-PCR.The apoptosis rate of SKOV3 cells in each group was detected by flow cytometry.The iron level of SKOV3 cells in these groups was detected by the kit.The protein expression levels of Nrf2,SLC7A11 and GPX4 in SKOV3 cells in these groups were detected by Western blot.Results:The proliferation rate(124.71±12.49%),the expression levels of Nrf2(1.15±0.12),SLC7A11(1.58±0.16),and GPX4(1.08±0.11)of the cells in the study group were all significantly higher than those of the cells in the control group.The apoptosis rate was(4.01±0.41%),the iron level(24.73±2.48)of the cells in the study group were all significantly lower than those of the cells in the control group(P<0.05).The proliferation rates of the cells in group B1,group B2,and group B3 were 74.22±7.43%,51.03±5.11%,and 35.23±3.53%,respectively,the Nrf2 level of the cells in group B1,group B2,and group B3 were 0.6

关 键 词：卵巢癌细胞 银杏素 Nrf2/SLC7A11/GPX4信号通路 增殖 凋亡 铁死亡 

分 类 号：R737.31[医药卫生—肿瘤]