rh-ES在血管正常化时间窗内联合顺铂对小鼠Lewis肺癌移植瘤的抗肿瘤效果  

The anti-tumor effect of rh-ES combined with cisplatin on mouse Lewis lung cancer xenografts in the normal vascularization time window

作　　者：徐姝玫 严沁[2] 李帅 黎露蔚 何朗 XU Shumei;YAN Qin;LI Shuai;LI Luwei;HE Lang(School of Medical and Life Sciences,Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China;Cancer Prevention and Treatment Institute of Chengdu,Department of Oncology,Chengdu Fifth People's HospitalThe Second Clinical Medical College,The Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China)

机构地区：[1]成都中医药大学医学与生命科学学院,四川成都610075 [2]成都市第五人民医院·成都中医药大学附属第五人民医院/第二临床医学院肿瘤科·成都市肿瘤防治所,四川成都611137 [3]成都中医药大学,四川成都610075

出　　处：《西部医学》2023年第8期1122-1128,共7页Medical Journal of West China

基　　金：中华国际医学交流基金会项目(Z-2014-06-19389);希思科-默沙东肿瘤研究基金项目(Y-MSD2020-0406);成都中医药大学“杏林学者”学科人才科研提升计划(YYZX2020021)。

摘　　要：目的 探索在血管正常化时间窗内顺铂(DDP)联合重组人血管内皮抑素(rh-ES)对小鼠Lewis肺癌移植瘤(LLC)的抗肿瘤治疗效果。方法 将30只SPF级LLC小鼠随机分为NS组、rh-ES组、DDP组、rh-ES+DDP (d_(1~3))组、rh-ES+DDP (d_(4~6))组、rh-ES+DDP(d_(7~9))组。NS组小鼠在第1至9天予以腹腔注射生理盐水(0.2 mL/d);rh-ES组小鼠在第1至9天予以腹腔注射rh-ES(5 mg·kg^(-1)·d^(-1));DDP组小鼠在第1至9天予以腹腔注射顺铂(2 mg·kg^(-1)·d^(-1));rh-ES+DDP(d_(1~3))、rh-ES+DDP(d_(4~6))、rh-ES+DDP(d_(7~9))组小鼠均分别在第1至9天予以腹腔注射rh-ES(5 mg·kg^(-1)·d^(-1)),并分别于对应时间段腹腔注射顺铂(2 mg·kg^(-1)·d^(-1))。记录6组LLC生长情况,通过病理免疫组化(IHC)检测肿瘤组织血管内皮生长因子(VEGF)、微血管密度(MVD)和DNp73α的情况。结果 与NS、rh-ES、DDP组相比,rh-ES+DDP组,肿瘤体积增加速度缓慢,VEGF、DNp73α表达率明显降低,MVD值显著降低,尤其在rh-ES+DDP(d_(4~6))组肿瘤生成体积最小(P<0.05),VEGF、DNp73α表达率最低(P<0.05),MVD值最低(P<0.05)。结论 重组人血管内皮抑素联合顺铂治疗对LLC肿瘤细胞生长的抑制效果明显优于单药治疗。Objective The objective of this study was to explore the antitumor effect of recombinant cisplatin(DDP)with human endostatin(rh-ES)combined on Lewis lung cancer(LLC)in the vascular normalization time window and its molecular mechanism.Methods Thirty LLC transplanted tumor mice were randomly divided into six groups:NS group,rh-ES group,DDP group,rh-ES+DDP(d1~d3)group,rh-ES+DDP(d4~d6)group,rh-ES+DDP(d7~d9)group,with 5 mice in each group.Mice in NS group was injected saline(0.2mL/d)in d1~d9 by intraperitoneal.Mice in rh-ES group were injected rh-ES(5mg/kg·d^(-1))in d1~d9 by intraperitoneal.Mice in DDP group were injected DDP(2mg/kg·d^(-1))in d1~d9 by intraperitoneal.Mice in rh-ES+DDP(d1~d3)group,rh-ES+DDP(d4~d6)group and rh-ES+DDP(d7~d9)group were injected rh-ES(5mg/kg·d^(-1))in d1~d9,and each group in d1~d3,d4~d6,d7~d9 respectively was injected DDP(2mg/kg·d^(-1))by intraperitoneal.The situation of tumor lung metastasis,changes of tumor VEGF,p73 and microvessel density(MVD)were detected by immunohistochemistry.Results Compared with each single drug group,the tumor volume of rh-ES combined with DDP group increased slowly and lowest expression rate of VEGF,MVD,p73,especially in rh-ES+DDP(d4-d6)group and the volume of LLC were the least(P<0.05).The expression rates of VEGF and p73 were the lowest(P<0.05),and the MVD value was the lowest(P<0.05).Conclusion The inhibitory effect of recombinant human endostatin combined with cisplatin on tumor cell growth is significantly better than that of monotherapy.

关 键 词：重组人血管内皮抑素 顺铂 肺癌 MVD VEGF DNp73α 

分 类 号：R734.2[医药卫生—肿瘤]