Inhibitory Effect of Angiogenesis Inhibitor TNP—470 on Human ACHN Renal Cell Carcinoma

Angiogenesis,the formation of new bloodvessels,is necessary for the growth of tumors andtheir metastasis.TNP- 470 is a synthetic analogueof fumagillin and has stronger antiangiogenic　 ac-tivity and less side- effects than fumagillin.Thiscompound has been reported to suppress the prolif-eration and metastasis of various kinds of tu-mors[1] . Using nude mice xenografts of ACHN hu-man renal cell carcinoma ( RCC) ,the presentstudyattempted to examine the action of TNP- 470 ongrowth,metastasi…

Inhibitory effect of angiogenesis inhibitor TNP-470 on human ACHN renal cell carcinoma

The contribution of angiogenesis inhibitor TNP- 4 70 to the growth and m etastasis of ACHN renal cell carcinom a (RCC) was studied. TNP- 4 70 (40 m g/ kg,every two days) was ad- ministrated to BABL / c nude m ice bearing ACHN RCC. The mice were sacrificed after a treatment duration of 31days and the weight and volum e of subcutaneous tum ors as well as foci of lung m etastasis were m easured.The microvascular density(MVD) of the tumor as well as the PCNA index and apoptotic index of the tum or cells were evaluated imm unohistochem ically. Result showed that the growth of ACHN RCC was suppressed significantly and none metastasis was ob- served in TNP- 4 70 - treated m ice. Compared with the control group,the MVD was decreased m arkedly (P<0 .0 1) and the apoptotic index was increased significantly (P<0 .0 1) in the treated group. The tumor volume was positively correlated to the MVD (r=0 .714 4 ,P<0 .0 1) and in- versely correlated to the apoptotic index(r=- 0 .86 0 7,P<0 .0 1) ,and MVD was conversely cor- related to the apoptotic index.It was determ ined that TNP- 4 70 could effectively inhibit angiogene- sis of ACHN RCC,which resulting in ischemia and hypoxia,leading to increased apoptosis,thus obviously suppressing the growth and metastasis of ACHN RCC in nude m ice.