实用肿瘤学杂志 ›› 2011, Vol. 25 ›› Issue (4): 319-324.doi: 10.3969/j.issn.1002-3070.2011.04.005

• 论著 • 上一篇    下一篇

自然杀伤细胞对小鼠HepS肝癌移植瘤的抑制作用研究

王艳辉1, 张南征1, 陈复兴2, 刘军权2, 周忠海2, 孙蕾清2   

  1. 1.徐州医学院附属淮海医院消化内科(徐州 221004);
    2.徐州医学院附属淮海医院实验科
  • 收稿日期:2011-03-30 出版日期:2011-04-25 发布日期:2012-02-21
  • 通讯作者: 张南征,E-mail:nanzhzhang@sina.com
  • 作者简介:王艳辉,女,(1985-),硕士,医师,从事消化内科治疗研究

Studies of natural killer cells on inhibition of transplanted Heps hepatoma in mice

WANG Yanhui1,ZHANG Nanzheng1,CHEN Fuxing2,LIU Junquan2,ZHOU Zhonghai2,SUN Leiqing2   

  1. 1.Department of Gastroenterology,Xuzhou Medical College Affiliated Huaihai Hospital,Xuzhou 221004;
    2.Biological Therapy Center,Xuzhou Medical College Affiliated Huaihai Hospital
  • Received:2011-03-30 Online:2011-04-25 Published:2012-02-21

摘要: 目的 研究自然杀伤(NK)细胞对原发性肝癌Heps移植瘤小鼠的治疗作用和机理。方法 建立小鼠移植性肝癌(Heps)实体瘤模型,随机分为生理盐水(NS)组、治疗1组(输注的NK细胞数为1×104/只)、治疗2组(输注的NK细胞数为1×105/只)和治疗3组(输注的NK细胞数为1×106/只),每组15只。接种肝癌细胞当天,分别于尾静脉注射不同数量的NK细胞,对照组注射NS。观测小鼠移植瘤体积及各组小鼠平均生存时间。各组于输注NK细胞后第15天分别处死2只小鼠,对移植瘤组织切片进行HE染色,用流式细胞术(FCM)检测脾细胞NK的含量;乳酸脱氢酶(LDH)释放法检测脾细胞杀伤活性。结果 接种移植瘤后第8天,治疗3组移植瘤的生长速度较其他组小鼠显著减慢(P<0.05)。第20天时治疗1组移植瘤体积明显小于对照组(P<0.05),治疗2组和3组移植瘤体积非常显著小于对照组(P<0.01)。治疗1组小鼠平均生存期明显长于对照组和治疗2、3组(P<0.01)。治疗1-3组脾细胞杀伤活性以及NK细胞的含量高于对照组(P<0.01)。结论 适量输注NK细胞可以有效抑制HepS肝癌移植瘤的生长,延长小鼠的生存期,为临床应用NK细胞治疗时数量的选择提供了实验依据。

Abstract: Objective To investigate the therapeutic effect of natural killer cells(NK cells)on mice of primary liver cancer Heps transplant tumor and discuss the mechanism.Methods Mouse models of the solid tumor of liver cancer(Heps)were established.Then the mice were randomly divided into four groups:Normal saline(NS)group,treatment group 1(1×104 NK cells/mouse),treatment group 2(1×105NK cells/mouse),treatment group 3(1×106NK cells/mouse).Each group has 15 mice.At the same day,different concentrations of NK cells were injected into the mice through the tail vein.The NS control group was administrated with the same volume of NS.Measure the implanted tumors volume as well as the mean survival time was calculated.Two mice from each group were sacrificed at the 15th day respectively.Tumor tissue samples were collected for routine pathological section,hematoxylin-eosin(H-E)staining.The spleen NK cells activity was estimated by LDH release assay;the activated NK cells in spleen were studied by flow cytometer(FACS).Results At the 8th day after inoculating,the growth situation of the tumor of group 3 was slower than that of other groups(P<0.05).At the 20th day,the volume of the tumors was markedly decreased in the treatment group 1(P<0.05),and the treatment group 2 and treatment group 3 are even more decreased compared with the NS group(P<0.01).Treatment group 1 mice′ average survival is obviously longer than NS group and treatment group 2,3(P<0.01).Compare with the NS control group′s NK cell in splenic,the treatment groups are obviously higher(P<0.01).The lethality of the splenic was obviously enhanced in the treatment groups than that in the NS control group.Conclusions Moderate NK cells can effectively restrain the growth of Heps hepatocellular carcinoma transplantation,and extend the mice survival.It′s a experimental basis for the clinical application of NK cells.

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