橄榄苦苷调节JAK2/STAT3信号通路对胆管癌细胞恶性生物学行为的影响OACSTPCD
Impacts of Oleuropein on the Malignant Biological Behavior of Cholangiocarcinoma Cells by Regulating the JAK2/STAT3 Signaling Pathway
目的:探讨橄榄苦苷(Ole)调节 Janus 激酶 2(JAK2)/信号转导和转录激活因子 3(STAT3)信号通路对胆管癌细胞恶性生物学行为的影响.方法:将对数生长期 HuCCT1 细胞分为 con-trol组、100μg/mL Ole组、200μg/mL Ole组、400μg/mL Ole 组、800μg/mL Ole 组和 Ole+JAK2/STAT3 信号通路激活剂(Colivelin)组,control组不做处理,100μg/mL Ole组、200μg/mL Ole组、400μg/mL Ole组、800μg/mL Ole组分别以 100、200、400、800μg/mL 的 Ole 干预 HuCCT1 细胞,Ole+Colivelin 组(分别以800μg/mL Ole和0.5μmoL/L Colivelin干预HuCCT1 细胞).CCK-8 法、平板克隆法、流式细胞术分别测定细胞活力、克隆及凋亡情况;Transwell 实验检测细胞迁移和侵袭;Western blot 法测定 JAK2/STAT3信号通路蛋白及凋亡蛋白表达.结果:100、200、400、800μg/mL Ole 组HuCCT1 细胞活力及克隆细胞数均低于control组,凋亡率高于control组,且变化趋势均呈 Ole 剂量依赖性(P<0.05);与 800μg/mL Ole组对比,Ole+Colivelin组HuCCT1 细胞活力及克隆细胞数均升高,凋亡率降低(P<0.05).与 control 组对比,100、200、400、800μg/mL Ole组HuCCT1 细胞迁移及侵袭数均呈 Ole 剂量依赖性降低(P<0.05);与800μg/mL Ole组对比,Ole+Colivelin组 HuCCT1 细胞迁移及侵袭数均升高(P<0.05).与 control 组对比,100、200、400、800μg/mL Ole组HuCCT1 细胞p-JAK2/JAK2、p-STAT3/STAT3、Bcl-2 蛋白表达均呈Ole剂量依赖性降低,Bax蛋白表达呈Ole剂量依赖性升高(P<0.05);与800μg/mL Ole组对比,Ole+Colivelin组HuCCT1 细胞 p-JAK2/JAK2、p-STAT3/STAT3、Bcl-2 蛋白表达均升高,Bax 蛋白表达降低(P<0.05).结论:Ole可能通过抑制JAK2/STAT3 信号通路活化进而抑制胆管癌细胞恶性生物学行为.
Objective:To investigate the impacts of Oleuropein(Ole)on the malignant biological behav-ior of cholangiocarcinoma cells by regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods:HuCCT1 cells in logarithmic growth phase were divided into control group,100μg/mL Ole group,200μg/mL Ole group,400μg/mL Ole group,800μg/mL Ole group,and Ole+JAK2/STAT3 signaling pathway activator(Colivelin)group.The control group was not trea-ted,and HuCCT1 cells in 100μg/mL Ole group,200μg/mL Ole group,400μg/mL Ole group,and 800μg/mL Ole groups were treated with 100,200,400,and 800μg/mL Ole,and the Ole+Colivelin group treated HuCCT1 cells with(800μg/mL Ole and 0.5μmoL/L Colivelin respectively).CCK-8 method,plate cloning method,and flow cytometry were applied to determine cell viability,cloning,and apoptosis,respectively.Tr-answell experiment was applied to detect cell migration and invasion.Western blot was applied to determine the expression of JAK2/STAT3 signaling pathway proteins and apoptotic proteins.Results:The HuCCT1 cell viability and number of cloned cells in the 100,200,400,and 800μg/mL Ole groups were lower than those in the control group,and the apoptosis rate was higher than that in the control group,the trend of change was Ole dose-dependent(P<0.05).Compared with the 800μg/mL Ole group,the HuCCT1 cell viability and number of cloned cells in the Ole+Colivelin group increased,while the apoptosis rate decreased(P<0.05).Compared with the control group,the migration and invasion of HuCCT1 cells in the 100,200,400,and 800μg/mL Ole groups showed an Ole dose-dependent decrease(P<0.05).Compared with the 800μg/mL Ole group,the migration and invasion of HuCCT1 cells in the Ole+Colivelin group increased(P<0.05).Compared with the control group,the protein expression of p-JAK2/JAK2,p-STAT3/STAT3,and Bcl-2 in HuCCT1 cells in the 100,200,400,and 800μg/mL Ole groups showed an Ole dose-dependent decrease,the protein expression of Bax showed an Ole dose-dependent increase(P<0.05).Compared with the 800μg/mL Ole group,the expression of p-JAK2/JAK2,p-STAT3/STAT3,and Bcl-2 proteins in HuCCT1 cells in the Ole+Colivelin group increased,the protein expression of Bax decreased(P<0.05).Conclusion:Ole may inhibit the malignant biological behavior of cholangiocarcinoma cells by inhibiting the activation of the JAK2/STAT3 signaling pathway.
郑伟;韩朝
陕西省核工业二一五医院普外二科,陕西 咸阳 712000
橄榄苦苷Janus激酶2/信号转导和转录激活因子3胆管癌恶性生物学行为
OleuropeinJanus kinase 2/signal transducer and activator of transcription 3Bile duct cancerMalignant biological behavior
《河北医学》 2024 (011)
1825-1830 / 6
陕西省2023年院级科研课题立项项目,(编号:215KYJJ-202316)
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