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

Abstract

The contribution of angiogenesis inhibitor TNP-470 to the growth and metastasis of ACHN renal cell carcinoma (RCC) was studied. TNP-470 (40 mg/kg, every two days) was administrated to BABL/c nude mice bearing ACHN RCC. The mice were sacrificed after a treatment duration of 31 days and the weight and volume of subcutaneous tumors as well as foci of lung metastasis were measured. The microvascular density (MVD) of the tumor as well as the PCNA index and apoptotic index of the tumor cells were evaluated immunohistochemically. Result showed that the growth of ACHN RCC was suppressed significantly and none metastasis was observed in TNP-470-treated mice. Compared with the control group, the MVD was decreased markedly (P<0.01) and the apoptotic index was increased significantly (P<0.01) in the treated group. The tumor volume was positively correlated to the MVD (r=0.7144,P<0.01) and inversely correlated to the apoptotic index (r=−0.8607,P<0.01), and MVD was conversely correlated to the apoptotic index. It was determined that TNP-470 could effectively inhibit angiogenesis 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 mice.

Keywords

renal cell carcinoma / TNP-470 / angiogenesis / animal experiment

References

[1] 1999, 19: 133

[2] GavrieliY, ShermanY, Ben-SassonS A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol, 1992, 119: 493-493

[3] GiavazziR, TarabolettiG. Angiogenesis and angiogenesis inhibitors in cancer. Forum (Genova), 1999, 9(3): 261-261

[4] StadlerW M, KuzelT, ShapiroC, et al. . Muti-institutional study of a angiogenesis inhibitor TNP-470 in metastatic renal carcinoma. J Clin Oncol, 1997, 17: 2541-2541

[5] FunahashiY, WakabyashiT, SembaT, et al. . Establishment of a quantitative mouse dorsal air sac model and its application to evaluate a new angiogenesis inhibitor. Oncol Res, 1999, 11(7): 319-319

[6] PenfoldC N, PatridgeM, RojasR, et al. . The role of angiogenesis in the spread of oral squamous cell carcinoma. Br J Oral Maxillofac Surg, 1996, 34: 37-37

[7] WangJ, LouP, HenkinJ, et al. . Selective inhibition of endothelial cell proliferation by fumagillin is not due to differential expression of methionine aminopeptidase. J Cell Bio Chem, 2000, 77(3): 465-465

[8] 1998, 30: 9