卡介苗联合DC-CIK细胞对裸鼠结肠癌生长及肝转移的抑制作用  

Inhibitory Effect of Bacillus Calmette-Guerin Vaccine Combined with DC-CIK Cells on Growth of Colon Cancer and Liver Metastases in BALB /c Nude Mice

作　　者：李雄兵[1] 刘汉锋[1] 蔡正文[1] 郑海平[1] 

机构地区：[1]广西医科大学第一附属医院肿瘤内科,南宁市530007

出　　处：《广西医学》2014年第4期424-427,共4页Guangxi Medical Journal

基　　金：广西壮族自治区面向农村和城市社区推广卫生适宜技术课题(S200803)

摘　　要：目的研究卡介苗联合树突状细胞(DC)及细胞因子诱导的杀伤细胞(CIK)对BALB/c裸鼠结肠癌肝转移的抑制作用。方法 60只BALB/c裸鼠腹腔内注射人结肠癌细胞株SW480建立结肠癌肝脏转移模型,随机分为对照组、DC-CIK组、卡介苗联合DC-CIK组(联合组),每组20只。联合组建模后第2天,鼠尾静脉注射卡介苗(12.5 mg/kg),隔日1次,共15次,并注射DC-CIK细胞免疫治疗,每周2次,共8次,DC-CIK组只注射DC-CIK细胞,对照组注射等量生理盐水。建模后30 d处死裸鼠,测量各组裸鼠原发灶的大小、肝转移瘤的数量,运用细胞角蛋白-18(CK-18)免疫组化单克隆抗体检测转移瘤组织来源;检测肿瘤转移灶的凋亡指数(AI)、肿瘤转移灶微血管密度(MVD)和血清血管内皮细胞生长因子(VEGF)浓度。结果各组脾脏的原发灶体积平均数分别为:对照组1.272 cm3,DC-CIK组1.096 cm3,联合组0.859 cm3;与DC-CIK组、对照组比较,联合组脾脏原发灶体积明显缩小(P均<0.05)。各组肝转移肿瘤为结肠腺癌CK-18(+);联合组肝转移瘤数量明显少于对照组和DC-CIK组(P均<0.05)。联合组肿瘤转移灶AI高于DC-CIK组、对照组(P均<0.05),血清VEGF浓度、MVD计数均明显低于DC-CIK组、对照组(P均<0.05)。结论卡介苗联合DC-CIK细胞或单独应用DC-CIK细胞均能明显抑制裸鼠结肠癌生长及肝转移,但卡介苗联合DC-CIK细胞的肿瘤抑制效果更好。Objective To investigate the inhibitory effect of DC-CIK cells combined with Bacille Calmette-Guerin vaccine（ BCG） on liver metastases in BALB / c nude mice with colon cancer. Methods Sixty BALB / c nude mice were given intraperitoneal injection of human colon cancer cell line SW480 cells to establish the mouse model of colon cancer and liver metastasis,they were randomly divided into control group,DC-CIK group,BCG combined with DC-CIK group（ combined group）,with 20 mice in each group. The mice in the combined group were injected with BCG（ 12.5 mg/kg）in tail vein once every another day for 15 times from the second day after establishing the model,and received the immunotherapy with injection of DC-CIK cells twice a week for 8 times,the mice in the DC-CIK group were injected with DC-CIK cells alone,the mice in the control group were injected with the same amount of normal saline. The nude mice were killed 30 days after modeling,Then the size of primary tumor and number of liver metastases were measured among nude mice of each group. Cytokeratin 18（ CK-18） was used to test the histological origin of metastatic tumor by immunohistochemistry. The apoptotic index（ AI） and microvessel density（ MVD） of metastasis focus as well as the serum level of vascular endothelial growth factor（ VEGF） were detected. Results The average volume of primary tumors implanted in spleens in three groups were 1. 272 cm^3（ control group）,1. 096 cm^3（ DC-CIK group）,0. 859 cm^3（ combined group）,respectively. The volume of primary tumor in the combined group was significantly smaller than those in the other two groups（ all P〈0. 05）. The liver metastases of each group were colonic adenocarcinoma[CK-18（ ＋） ].The number of liver metastasis in the combined group was significantly fewer than those in the control group and DC-CIK group（ all P〈0. 05）. The AI in the combined group was significantly higher than those in the other two groups（ allP〈0. 05）. The serum level of VEGF and MVD of

关 键 词：结肠癌 肝转移 卡介苗 树突状细胞 生物治疗 裸鼠 

分 类 号：R735.35[医药卫生—肿瘤]