摘要
本研究探讨不同浓度的IL-6在弥漫大B淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的作用,以及是否通过JAK/STAT3信号通路介导细胞的凋亡增殖与侵袭迁移能力。使用人DLBCL细胞系OCI-LY8作为模型,通过药物干预IL-6或转染质粒敲除STAT3基因。通过CCK8法检测细胞活力,并使用流式细胞术测定各组细胞的凋亡率,研究IL-6对DLBCL细胞增殖凋亡能力的影响。使用Transwell小室和划痕实验,检测细胞侵袭和迁移能力,研究不同浓度IL-6对DLBCL转移能力的作用。使用Western blotting检测JAK,STAT3以及其下游凋亡相关的B细胞淋巴瘤2(B cell lymphoma 2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2-associated X protein,Bax)和生存素(survivin)蛋白的表达情况。Western blotting结果显示IL-6可以有效激活JAK/STAT3通路,并上调抗凋亡蛋白Bcl-2和生存素,下调促凋亡蛋白Bax,从而抑制OCI-LY8凋亡。此外,IL-6通过激活STAT3也能提高OCI-LY8的侵袭与迁移能力。而IL-6的作用在IL-6抑制剂LMT-28处理或STAT3敲除后被逆转。IL-6能通过激活JAK/STAT3信号通路,增强DLBCL细胞株OCI-LY8的侵袭和迁移能力,并增强其抗凋亡能力。这些发现揭示IL-6在DLBCL发生中的作用,为DLBCL的治疗提供了新的靶点和理论依据。
This study aimed to investigate the role of IL-6 in diffuse large B-cell lymphoma(DLBCL)and the role of IL-6 on cell apoptosis,proliferation,invasion and migration via the JAK/STAT3 signaling pathway.OCI-LY8 cell line was used as a DCBCL model and drug intervention of IL-6 or STAT3 gene silencing were used to assess the effect of IL-6 and STAT3 on OCI-LY8 cells.Cell viability was detected by CCK8 assay and apoptosis rate was determined by flow cytometry to study the effect of IL-6 on the proliferation and apoptosis of DLBCL cells.Transwell assay and scratch assay were used to detect cell invasion and migration capacity and elucidate the effect of different IL-6 concentrations on DLBCL migration.The expressions of JAK,STAT3 and the downstream apoptosis-related B cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax)and survivin proteins were detected by Western blotting.Western blotting showed that IL-6 up-regulated anti-apoptotic proteins Bcl-2 and survivin,and downregulated pro-apoptotic protein Bax by activating the JAK/STAT3 pathway,thereby inhibiting OCI-LY8 apoptosis.IL-6 could also enhance the invasion and migration of OCI-LY8 by activating STAT3.The effect of IL-6 was reversed upon IL-6 inhibitor LMT-28 treatment or STAT3 silencing.IL-6 enhanced the invasion and migration capacity of OCI-LY8 DLBCL cells by activating the JAK/STAT3 signaling pathway,as well as increasing their anti-apoptosis ability.Together,these findings reveal that IL-6 promotes DLBCL development via the JAK/STAT3 pathway,which provides a new potential target and theoretical basis for DLBCL treatment.
作者
赵明哲
王丽莉
ZHAO Mingzhe;WANG Lili(Department of Hematology,Jinhua Municipal Central Hospital,Jinhua 321000,China)
出处
《现代免疫学》
2025年第5期585-592,共8页
Current Immunology
基金
金华市科技计划项目(2022-4-094)。
