三羧氨基喹啉对人口腔癌裸鼠移植瘤的抗血管生成作用与其调节巨噬细胞分泌细胞因子的关系  

Antiangiogenesis effect of linomide in treatment of transplanted human oral carcinoma in nude mice and its relations to regulation on cytokine secretion of macrophage

作　　者：傅其宏[1] 余海[2] 王青青[3] 吴求亮[1] 

机构地区：[1]浙江大学医学院附属第一医院,浙江杭州310003 [2]浙江大学肿瘤研究所,浙江杭州310009 [3]浙江大学免疫学研究所,浙江杭州310031

出　　处：《浙江大学学报（医学版）》2002年第4期273-276,280,共5页Journal of Zhejiang University(Medical Sciences)

摘　　要：目的 :观察三羧氨基喹啉 ( Linom ide)对人口腔癌裸鼠移植瘤的治疗作用 ,探讨其抗血管生成作用与调节巨噬细胞分泌细胞因子的关系。方法 :建立人舌癌裸鼠移植瘤模型 ,观察 Linom ide对肿瘤生长的抑制作用 ,采用免疫组化染色检测 L inomide治疗组和对照组荷瘤裸鼠的肿瘤微血管密度 ( MV D)的变化 ,采用 ELISA方法检测Linom ide对巨噬细胞分泌促血管因子 TN F- α及血管抑制因子 G M- CSF功能的影响。结果 :10 0 m g/ kg· d- 1、50mg/ kg· d- 1Linom ide腹腔注射组、对照组裸鼠瘤重分别为 ( 0 .4 7± 0 .2 5) g、( 0 .92± 0 .30 ) g、( 1.75± 0 .38) g,治疗组瘤重明显降低 ( P<0 .0 1)。治疗组瘤组织 M VD明显减低 ,与对照组相比 ,50 m g/ kg· d- 1和 10 0 m g/ kg· d- 1Linom ide治疗组的 MV D分别减少了 38.2 %和 57.8%。 Linom ide治疗组腹腔巨噬细胞分泌 TN F-α的水平与对照组比较 ,受到明显抑制 ( P<0 .0 5)。 L inom ide体外处理小鼠巨噬细胞系 RA W 2 6 4.7也可明显抑制其分泌 TN F-α的水平 ( P <0 .0 5) ,并存在剂量效应关系。结论 :Linom ide可有效抑制人舌鳞状细胞癌裸鼠移植瘤的生长 ,降低肿瘤微血管密度 ,抑制巨噬细胞分泌 T NF-α可能是其一个重要的抗血管生成机制。Objective: To investigate the antiangiogenesis effect of linomide in treatment of transplanted human squamous cell carcinoma of tongue in BALB/C nude mice and to study its relations to regulation on cytokine secretion of macrophages. Methods: An animal model was established by inoculating the human squamous cell carcinoma cell line Tca8113 into the BALB/c nu/nu nude mice. The mice were randomly divided into three groups and received linomide therapy. The microvessel density (MVD) in the tumor tissue was investigated by immunohistochemistry The productions of TNF α and GM CSF of peritoneal macrophages derived from the tumor bearing nude mice and cultured murine macrophage cell line RAW264.7 after linomide treatment were detected by ELISA assay. Results: It showed that the tumor weight of mice injected intraperitoneally with 100 mg/kg·d -1 , 50 mg/kg·d -1 linomide and mice of control group were 0.47±0.25g, 0.92±0.30g and 1.75±0.38g, respectively. The microvessel density (MVD) in tumor tissue from mice treated with linomide 100 mg/kg·d -1 , 50 mg/kg·d -1 decreased 38.2%, 57.8% respectively when compared with that in mice of control group. After linomide treatment, the function of TNF α secretion of peritoneal macrophages from tumor bearing nude mice was significantly inhibi ted when compared with macrophages from untreated mice. And linomide inhibited the release of TNF α of RAW264.7 cells in a dose dependent manner. Conclusion: It indicats that linomide can effectively inhibit the growth of human squamous carcinoma of tongue in nude mice and decrease the microvessel density in the tumor tissue. The affection of release of antiangiogenic factor TNF α of macrophage may be an important mechanism of antitumor activity of linomide.

关 键 词：三羧氨基喹啉 口腔癌 裸鼠移植瘤 抗血管生成作用 巨噬细胞 新生血管化 病理学 肿瘤坏死因子 

分 类 号：R739.8[医药卫生—肿瘤]