IL-15细胞因子影响非肌层浸润型膀胱癌进展的机制  

Mechanism of the impact of IL-15 cytokines on the progression of nonmuscle-invasive bladder cancer

作　　者：王婷 WANG Ting(Laboratory Department,Henan Veterans Rehabilitation Hospital,Zhengzhou 450014,CHN)

机构地区：[1]河南省老干部康复医院检验科,郑州450014

出　　处：《河南大学学报（医学版）》2024年第6期401-406,共6页Journal of Henan University:Medical Science

摘　　要：目的:探究IL-15对非肌层浸润性膀胱癌进展影响的作用机制。方法:在细胞模型上,使用IL-15细胞因子处理小鼠脾脏来源的淋巴细胞,将处理后的淋巴细胞和膀胱癌肿瘤细胞MB49、T24共培,通过MTT法检测细胞凋亡情况评价IL-15处理后的淋巴细胞对肿瘤细胞的细胞毒性。在动物肿瘤模型上,使用硝酸银腐蚀小鼠膀胱,注射小鼠膀胱癌细胞MB49建立小鼠膀胱癌原位模型,分为空白组、IL-15组、IL-15和BCG联用组,治疗3周后比较不同组别的肿瘤重量,通过Q-PCR检测IL-15处理后脾脏淋巴细胞MHCⅠ、MHCⅡ、TNF-α和IFN-γ的mRNA表达情况,使用免疫组化染色检测不同治疗方案肿瘤组织中CD8阳性T细胞的浸润情况。结果:IL-15处理后,IL15浓度为100ng/mL时,对照组细胞存活率(97.05±0.15)%,T24细胞存活率(36.6±0.40)%,MB49细胞存活率(35.3±0.7)%(MB49:t=3.627,P=0.0361;T24:t=3.642,P=0.0357),脾脏来源的淋巴细胞表现出对膀胱癌肿瘤细胞显著增强的细胞毒性,并且具有更高的MHCⅠ、MHCⅡ、TNF-α和IFN-γ的mRNA表达(MHCI:P<0.0001,t=76.49;MHCⅡ:P<0.0001,t=101.2;TNFα:P<0.0001,t=70.99;IFN-γ:P<0.0001,t=116.9);使用IL-15或BCG和IL-15联合治疗,能够显著地抑制肿瘤进展,肿瘤组织中具有更多地CD8阳性T细胞浸润。结论:IL-15细胞因子通过诱导激活CD8阳性T细胞抑制膀胱癌肿瘤进展。Objective:To investigate the mechanism of the impact of IL-15 on progress of non-muscle-invasive bladder cancer.Methods:On the cellular model,IL-15 cytokine was used to treat lymphocytes derived from mouse spleens.The treated lymphocytes and bladder cancer cells MB49and T24 were co-cultured,and the apoptosis of tumor cells by IL-15-treated lymphocytes was evaluated using the MTT assay.In the animal model,silver nitrate was used to corrode the mouse bladder,and MB49 bladder cancer cells were injected to establish an in situ model of mouse bladder cancer.The mice were divided into blank group,IL-15 group,and IL-15combined with BCG group,and the tumor weight was compared after three weeks of treatment.The mRNA expression of MHC Ⅰ,MHC Ⅱ,TNF-a,and IFN-yin splenic lymphocytes treated with IL-15 was detected usingQ-PCR.Immunohistochemicalstaining was used to detect the infiltration of CD8-positive T cells in tumor tissues under different treatment regimens.Results:After treatment with IL-15,when the IL-15concentration is 100 ng/ml,the control group cell survival rate(97.05±0.15)%,T24 cell survival rate(36.6±0.40)%,and MB49 cell survival rate(35.3士0.7)%(MB49:t=3.627,P=0.0361;T24:t=3.642,P=0.0357),the splenic lymphocytes exhibited significantly enhanced cytotoxicity against bladder cancer cells.Furthermore,they showed increased mRNA expression of MHC Ⅰ,MHC Ⅱ,TNF-a,and IFN-γ(MHC Ⅰ:p<0.0001,t=76.49;MHC Ⅱ:P<0.0001,t=101.2;TNFα:P<0.0001,t=70.99;IFN-γ:P<0.0001,t=116.9).Treatment with IL-15 or BCG and IL-15combined can significantly inhibit tumor progression and increase CD8-positive T cell infiltration in the tumor tissue.Conclusion:IL-15cytokines suppress the progression of bladder cancer tumors by inducing the activation of CD8^(+)T cells.

关 键 词：IL-15 非肌层浸润膀胱癌 免疫细胞激活 

分 类 号：R73[医药卫生—肿瘤]