血管生成抑制剂TNP-470对ACHN肾癌的抑制作用  

Experiment study on the inhibitory effect of TNP-470 on ACHN renal cell carcinoma in mouse

作　　者：曾进[1] 梅伟[1] 黄海鹏[1] 李晓东[1] 孔鹏[1] 叶章群[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院泌尿外科,武汉430030

出　　处：《中华实验外科杂志》2004年第10期1231-1232,i002,共3页Chinese Journal of Experimental Surgery

摘　　要：目的　探讨血管生成抑制剂TNP 470抑制ACHN肾癌生长和转移的作用机制。方法　采用TNP 470 (4 0mg·kg-10 .2ml-1)皮下注射治疗ACHN肾癌荷瘤裸鼠 ,观察肿瘤生长情况。 3 1d后处死裸鼠 ,测定肿瘤体积 ;采用免疫组织化学方法和原位缺口末端标记 (TUNEL) ,观察TNP 470对肺转移、肿瘤微血管密度 (MVD)、肿瘤细胞增殖指数 (PI)和凋亡指数 (AI)的影响。结果　治疗组生长明显减慢 [重量 (2 70 .0 0± 62 .3 5 )mgvs (63 0 .0 0± 12 3 .65 )mg ;体积 (12 6.5 4±45 .12 )mm3 vs (3 16.16± 60 .2 8)mm3 ,P <0 .0 1] ,MVD明显减少 (5 .65± 2 .3 1vs 12 .0 0± 3 .78,P <0 .0 1) ,AI明显增加 (5 .0 8± 1.87vs 1.75± 0 .83 ,P <0 .0 1)。MVD与AI呈负相关 ,与肿瘤体积呈正相关 ,相关系数分别为r =-0 .860 7,P <0 .0 1;r =0 .714 4,P <0 .0 1。AI与肿瘤体积呈负相关 (r =-0 .85 40 ,P <0 .0 5 )。结论　TNP 470对ACHN肾癌有显著的抗血管生成的作用 ,对肿瘤的生长和转移有明显的抑制作用 ,其机制可能为抑制肿瘤血管生成使之缺血缺氧 。Objective To study the effect of Angiogenesis inhibitior TNP-470 on the growth and metastasis of ACHN renal cell carcinoma.Methods TNP-470 (40 mg/kg,once every other day,s.c.) was administrated to BALB/C nude mice bearing ACHN renal cell caricinoma.Thirty-one dayslater,the mices were sacrificed.The weight and volume of tumors as well as foci of the lung metastasis were measured.The angiogenesis and growth of tumor,the proliferation index (PI) and the apoptosis index (AI) in tumor cells were studied by immunohistochemistry and TUNEL.Results The growth of the treated group was significantly suppressed [weight (270.00± 62.35) mg vs (630.00± 123.65) mg,volume (126.54± 45.12) mm 3 vs (316.16± 60.28) mm 3, P< 0.01] .MVD of tumors in the treated group was lower than that in control group (5.65± 2.31 vs 12.00± 3.78, P< 0.01) and AI in the treated group was higher than that in the control group (5.08± 1.87 vs 1.75± 0.83, P< 0.01).MVD had an inverse correlation to AI and the volume of tumors with r being -0.860?7 (P< 0.01) and -0.714?4 (P< 0.01), respectively.AI had an inverse correlation to the volume of tumors (r= -0.854?0, P< 0.05). Conclusion TNP-470 has remarkable action of the antiangiogenesis,and can obviously inhibit the angiogenesis and the growth and metastasis of ACHN renal cell carcinoma in the nude mice probably induced by hypoxia-mediated,which leading to the increasing of the apoptosis in tumor cells.

关 键 词：肾癌 血管生成 脱噬作用 抑制作用 

分 类 号：R737.11[医药卫生—肿瘤]