白细胞介素-12抗NK/T细胞淋巴瘤的活性及其机制研究  

Anti-NK/T-cell lymphoma activity of interleukin-12 and its mechanisms

作　　者：王媛[1] 惠双[1] 张成辉[1] 郭宏强 李敏[3] 郑芝欣[3] WANG Yuan;HUI Shuang;ZHANG Cheng-hui;GUO Hong-qiang;LI Min;ZHENG Zhi-xin(Dept of Oncology,Nanyang Central Hospital,Nanyang Henan 473000,China;Cancer Ward,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Pharmaceutics Room,Nanyang Central Hospital,Nanyang Henan 473000,China)

机构地区：[1]南阳市中心医院肿瘤内科,河南南阳473000 [2]郑州大学第一附属医院肿瘤综合病区,河南郑州450000 [3]南阳市中心医院药学室,河南南阳473000

出　　处：《中国药理学通报》2020年第3期365-371,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金项目(No 81101797)。

摘　　要：目的研究白细胞介素-12(IL-12)的抗NK/T细胞淋巴瘤活性及机制。方法培养NK/T细胞淋巴瘤的YTS细胞株并分为对照组、IL-12组、NC siRNA组、JAK2 siRNA组、空白质粒组、JAK2表达质粒组,用含有0.625、1.25、2.5、5.0、10.0、20.0 ng·mL^-1 IL-12的培养基处理或转染NC siRNA、JAK2 siRNA、空白质粒、JAK2表达质粒,检测细胞活力、细胞凋亡、细胞周期及细胞中JAK2及STAT3的表达;选择C57小鼠并建立移植瘤模型,随机分为对照组及IL-12组后,测定移植瘤质量及JAK2、STAT3的表达。结果在YTS细胞中,IL-12以及JAK2 siRNA能够抑制细胞活力、细胞周期及细胞中p-JAK2、p-STAT3的表达,诱导细胞凋亡(P<0.05);转染JAK2的表达质粒能够使20.0 ng·mL^-1的IL-12抑制细胞活力、细胞周期、细胞中p-JAK2、p-STAT3表达及诱导细胞凋亡的作用减弱;在移植瘤小鼠中,IL-12干预后,移植瘤质量及移植瘤中p-JAK2、p-STAT3的表达均明显下降(P<0.05)。结论IL-12具有抗NK/T细胞淋巴瘤的活性且其机制与抑制JAK2/STAT3信号通路的激活有关。Aim To study the anti-NK/T-cell lympho-ma activity and mechanism of interleukin-12(IL-12).Methods YTS cell lines of NK/T cell lymphoma were cultured and randomly divided into control group,IL-12 group,NC siRNA group,JAK2 siRNA group,blank plasmid group and JAK2 expression plasmid group,treated with medium with different concentra-tions of IL-12(0.625,1.25,2.5,5.0,10.0,20.0 ng·mL^-1)and transfected with NC siRNA,JAK2 siRNA,blank plasmid,JAK2 expression plasmid.Then cell viability,apoptosis,cell cycle and the ex-pression of JAK2 and STAT3 were detected.C57 mice were selected and randomly divided into control group and IL-12 group.After intervention,the quality of transplanted tumors and the expression of JAK2 and STAT3 were measured.Results In YTS cells,IL-12 or JAK2 siRNA could inhibit cell viability,cell cycle,the expression of p-JAK,p-STAT3,and induced the apoptosis(P<0.05);transfection of JAK2 expressed plasmid could weaken the effect of 20.0 ng·mL^-1 IL-12 on viability,cell cycle,apoptosis and the expres-sion of p-JAK,p-STAT3(P<0.05);in xenotrans-planted tumor mice intervened with IL-12,the weight of xenotransplanted tumor and the expression of p-JAK,p-STAT3 in xenotransplanted tumor significantly decreased(P<0.05).Conclusions IL-12 has anti-NK/T cell lymphoma activities and its mechanism is related to the inhibition of the activation of JAK2/STAT3 signaling pathway.

关 键 词：NK/T细胞淋巴瘤 白细胞介素-12 Janus蛋白质酪氨酸激酶2 信号转导和转录活化蛋白3 凋亡 细胞周期 

分 类 号：R-332[医药卫生] R329.25