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.


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.
Emoto
M
M
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Japan. mm036123@msat.fukuoka-u.ac.jp
Ishiguro
M
M
Iwasaki
H
H
Kikuchi
M
M
Kawarabayashi
T
T
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002296:Carcinosarcoma / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D003510:Cyclohexanes; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000096:biosynthesis* / Q000378:metabolism; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000903:Antibiotics, Antineoplastic; D003470:Culture Media; D003510:Cyclohexanes; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077609:O-(Chloroacetylcarbamoyl)fumagillol