重组人血管内皮抑素联合顺铂不同时相治疗小鼠Lewis肺癌移植瘤疗效观察  

Effect of recombinant human endostatin combined with cisplatin on different stages of Lewis lung cancer xenograft in mice

作　　者：何朗 刘康[3] 陈梅 刘涛[5] 吴迅[4] 王晓珊[6] 陈红[7,8] HE Lang;LIU Kang;CHEN Mei;LIU Tao;WU Xun;WANG Xiao-shan;CHEN Hong(Fifth People's Hospital of Chengdu,Second Clinical Medicine School of Chengdu University of TraditionalChinese Medicine,Chengdu611130,P.R.China;North Sichuan Medical College,Nanchong637000,P.R.China;Department of Cardiovascular Medicine,Second Clinical Medical College of North Sichuan Medical College,Nanchong Central Hospital,Nanchong637000,P.R.China;Department of Oncology,Sichuan Academy of Medical Sciences,Sichuan Provincial People's Hospital,Nanchong610072,P.R.China;Department of Traditional Chinese Medicine,Affiliated Hospital of North Sichuan Medical College,Nanchong637000,P.R.China;Department of Oncology and Traditional Chinese Medicine,Sichuan Cancer Hospital,Chengdu610072,P.R.China)

机构地区：[1]成都市第五人民医院,成都中医药大学第二临床医学院肿瘤科,四川成都611130 [2]成都市第五人民医院,成都中医药大学第二临床医学院呼吸科,四川成都611130 [3]川北医学院组织工程与干细胞研究所,四川南充637000 [4]川北医学院临床医学系,四川南充637000 [5]川北医学院第二临床医学院,南充市中心医院心血管内科,四川南充637000 [6]四川省医学科学院,四川省人民医院肿瘤科,四川成都610072 [7]川北医学院附属医院中医科,四川南充637000 [8]四川省肿瘤医院中医肿瘤科,四川成都610072

出　　处：《中华肿瘤防治杂志》2018年第20期1422-1428,共7页Chinese Journal of Cancer Prevention and Treatment

基　　金：2014四川省科技厅项目(2014SZ0020-7);2017年四川省卫计委项目(17PJ490);2017年四川省医学会项目(S17042);2016年四川省教育厅项目(17ZA0176);2015年四川省教育厅项目(15ZB0194);2015年川北医学院博士启动基金(CBY15-QD09);2014年南充市科技局项目(14A0051)

摘　　要：目的 抗血管生成药物使用后可使肿瘤内部血管趋于正常化,在血管正常化窗口期内联合抗肿瘤药物可增强抗肿瘤疗效。本研究初步探讨重组人血管内皮抑素联合顺铂(cisplatin,DDP)在不同用药时相治疗Lewis肺癌细胞(Lewis lung cancer cell,LLC)移植瘤鼠的不同疗效及肿瘤细胞凋亡情况。方法 30只LLC移植瘤小鼠随机分为生理盐水组。重组人血管内皮抑素组。DDP组。重组人血管内皮抑素+DDP(d1~d3)组。重组人血管内皮抑素+DDP(d4~d6)组。重组人血管内皮抑素+DDP(d7~d9)组,共6组,每组5只。测量不同组别小鼠体质量变化,计算抑瘤率。HE染色观察不同组别移植瘤肿瘤细胞坏死状况。TUNEL法检测不同组别肿瘤细胞凋亡情况。结果 实验结束时(d13),生理盐水组。DDP组。重组人血管内皮抑制素组。重组人血管内皮抑素+DDP(d1~d3)组。重组人血管内皮抑素+DDP(d4~d6)和重组人血管内皮抑素+DDP(d7~d9)组小鼠体质量分别为(19.40±1.29)、(18.42±0.76)、(19.05±0.74)、(18.59±0.71)、(17.57±0.82)和(18.87±0.63)g,抑瘤率分别为15.91%、14.26%、28.65%、53.91%和24.61%。其中重组人血管内皮抑素+DDP(d4~d6)组小鼠体质量最小(P>0.05),肿瘤生长最慢。抑瘤率最高(F=3.30,P<0.001),肿瘤坏死最为明显。TUNEL染色后肿瘤凋亡细胞分散于癌细胞间,胞体变小,呈黄绿色。生理盐水组。DDP组。重组人血管内皮抑制素组。重组人血管内皮抑素+DDP(d1~d3)组。重组人血管内皮抑素+DDP(d4~d6)和重组人血管内皮抑素+DDP(d7~d9)组凋亡指数分别为(1.80±0.80)%、(2.98±1.43)%、(3.18±1.57)%、(3.88±1.60)%、(6.80±1.96)%和(4.05±1.68)%,其中重组人血管内皮抑素+DDP(d4~d6)组凋亡指数最高,F=24.39,P<0.001。结论 重组人血管内皮抑素使用后的不同时机联合用药将出现不同的治疗效果,但在用药后d4~d6这一血管正常化时间窗联合给药能显著增加抗瘤效果,促进肿瘤细胞凋亡。OBJECTIVE The aim of this study was to investigate the effects of recombinant human endostatin combined with cisplatin(DDP)on the treatment of Lewis lung carcinoma(LLC)transplanted mice in different phases and theapoptosis of tumor cells.METHODS Thirty LLC transplanted tumor mice were randomly divided into 6groups,5rats ineach group.Normal saline group:0.2 ml/d,intraperitoneal injection,d1 -d9;recombinant human endostatin group:5mg/(kg·d),intraperitoneal injection,d1-d9;DDP group:2mg/(kg·d),intraperitoneal injection,d1-d3;recombinanthuman endostatin+DDP(d1-d3):recombinant human endostatin 5mg/(kg·d),intraperitoneal injection,d1-d9;DDP2mg/(kg·d),intraperitoneal injection,d1-d3;recombinant human endostatin+DDP(d4-d6):recombinant human vascular endostatin 5mg/(kg·d),intraperitoneal injection,d1-d9;DDP 2mg/(kg·d)-1,intraperitoneal injection,d4-d6;recombinant human endostatin,abdominal cavity injection,d1-d9,DDP 2mg/(kg·d),intraperitoneal injection,d7-d9.The changes of weight in different groups of mice were measured,and anti-tumor rate was calculated on tumor weight inmice.Transplanted tumor necrosis was performed using hematoxylin-eosin staining.Apoptosis of tumor was tested byTUNEL.RESULTS On d13,the mouse weight of normal saline group,DDP group,recombinant human endostatin group,recombinant human endostatin+DDP(d1-d3)group,recombinant human endostatin+ DDP(d4-d6)group and recombinant human endostatin+DDP(d7-d9)group were(19.40±1.29),(18.42±0.76),(19.05±0.74),(18.59±0.71),(17.57±0.82)and(18.87±0.63)g,respectively,while tumor inhibition rates of those groups were 15.91%,14.26%,28.65%,53.91%and 24.61%.The mouse weight of recombinant human endostatin+DDP(d4-d6)group was the heaviest(P>0.05),and the tumor inhibition rate was the highest(F=3.30,P<0.001).The TUNEL staining results showedthe apoptotic cells were dispersed between cancer cells,and the cell bodies were yellow green.The apoptosis index of thosegroups were(1.80±0.80)%,(2.98±1.43)%,(3.18±1.57)%,(3.88±1.60)%,(6.80±1.96)% and (4.05±1.68)%,resp

关 键 词：重组人血管内皮抑素 LEWIS肺癌细胞 血管正常化 疗效 凋亡 

分 类 号：R734.2[医药卫生—肿瘤]