TNP-470 inhibits growth and the production of vascular endothelial growth factor of uterine carcinosarcoma cells in vitro.

BACKGROUND: Carcinosarcoma is the most aggressive neoplasm among the known uterine malignancies. Most patients who are affected with this biphasic neoplasm hardly show any response to common anti-cancer drugs or radiotherapy and thus they tend to show an extremely poor prognosis. This is the first study to examine the inhibitory and anti-angiogenic effects of angiogenesis inhibitor TNP-470, a synthetic analogue of fumagillin, for human uterine carcinosarcoma in vitro.
MATERIALS AND METHODS: The direct growth-inhibitory effect of TNP-470 was examined by an MTT assay in vitro. The levels of vascular endothelial growth factor (VEGF) in the culture supernate of TNP-470 treated FU-MMT-1 cells were also analyzed by an enzyme-linked immunosorbent assay (ELISA). The VEGF expression of TNP-470 treated FU-MMT-1 cells was also immunohistochemically examined using an anti-VEGF antibody.
RESULTS: TNP-470 inhibited the growth of FU-MMT-1 cells in vitro. The level of VEGF in the culture supernatant of TNP-470 treated FU-MMT-1 cells was significantly lower than that of the control (TNP-470 untreated FU-MMT-1 cells) in vivo. The expression of VEGF in TNP-470 treated FU-MMT-1 cells immunocytochemically decreased in comparison to that of the control TNP-470 untreated FU-MMT-1 cells).
CONCLUSIONS: Our in vitro findings suggest that this angiogenesis inhibitor, TNP-470, might be a novel therapeutic agent for uterine carcinosarcoma. However, further in vivo experimental studies using TNP-470 for this tumor will be necessary before any definitive conclusions can be made.