LPM3480226联合索拉菲尼抗小鼠肾癌Renca  

Anti-tumor Effects of IDO Inhibitor LPM3480226in Combination with Sorafenib on Renca-bearing Mice

作　　者：郑爽 李晓鹏 刘塑杰 杜广营[1] 田京伟[1] ZHENG Shuang;LI Xiao-peng;LIU Su-jie;DU Guang-ying;TIAN Jing-wei(School of Pharmacy,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drug in Universities of Shandong,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Yantai University,Yantai 264005,China)

机构地区：[1]烟台大学药学院,烟台大学新型制剂与生物技术药物研究山东省高校协同创新中心,烟台大学分子药理和药物评价教育部重点实验室,山东烟台264005

出　　处：《烟台大学学报（自然科学与工程版）》2022年第2期184-190,共7页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：山东省重大科技创新工程基金资助项目(2019JZZY020307)。

摘　　要：本文旨在研究吲哚胺2,3-双加氧酶(IDO)抑制剂LPM3480226联合多靶点抗血管生成药物索拉菲尼的抗肿瘤效应及其潜在作用机制。采用小鼠肾癌Renca移植瘤模型,经口灌胃给予200 mg/kg LPM3480226(2次/d),15 mg/kg索拉菲尼(1次/d),或二者联用,连续19 d,观察荷瘤小鼠体重、肿瘤体积、肿瘤重量、肿瘤浸润CD3^(+)CD4^(+)和CD3^(+)CD8^(+)T细胞比例以及肿瘤组织CD34阳性微血管密度(CD34-MVD)。结果显示,LPM3480226与索拉菲尼联用时动物体重未显著降低,二者联用的抗肿瘤作用优于药物单用,且肿瘤组织内CD3^(+)CD4^(+)、CD3^(+)CD8^(+)效应T细胞比例显著提高,CD34-MVD水平显著降低。本研究表明,LPM3480226与索拉菲尼在Renca小鼠模型中具协同抗肿瘤作用,与增加肿瘤浸润淋巴细胞比例和降低血管形成有关。基于IDO抑制剂的免疫治疗与抗血管生成药物联用可能成为提高肿瘤临床治疗效果的重要策略之一。The aim of this study is to study the anti-tumor effect of indoleamine 2,3-dioxygenase(IDO)inhibitor LPM3480226 in combination with multi-target antiangiogenic drug sorafenib and its potential mechanism.The model of Renca transplanted tumor of renal cell carcinoma in mice is used.200 mg/kg LPM3480226(twice a day),15 mg/kg Sorafinib(once a day),or both are given orally for 19 days.The body weight,tumor volume,tumor weight,the proportion of CD3^(+)CD4^(+)and CD3^(+)CD8^(+)T cells in tumor infiltration and CD34 positive microvessel density(CD34-MVD)in tumor tissue are observed.The results show that the body weight of animals don't decrease significantly when LPM3480226 is used in combination with Sorafinib,and the anti-tumor effect of the combination of sorafenib and sorafenib is better than that of drug alone,and the proportion of CD3^(+)CD4^(+)and CD3^(+)CD8^(+)effector T cells in tumor tissue increases significantly,while the level of CD34-MVD decreases significantly.The study indicates that LPM3480226 and sorafenib have synergistic anti-tumor effect in Renca mouse model,which is related to the increase of the proportion of tumor infiltrating lymphocytes and the decrease of angiogenesis.It also suggests that the combination of IDO inhibitor-based immunotherapy with anti-angiogenic drugs might serves as a new potential strategy for cancer treatment.

关 键 词：LPM3480226 吲哚胺2 3-双加氧酶 索拉菲尼 免疫治疗 抗血管生成治疗 

分 类 号：R966[医药卫生—药理学]