Short-term effects of TNP-470 in combination with cisplatin in the rat model of bladder cancer.
OBJECTIVE
To investigate the short-term effects of TNP-470 in combination with cisplatin in a rat model of bladder cancer.


METHODS
Following treatment of TNP-470 with or without cisplatin for 7 days, the states of angiogenesis, apoptosis and cell proliferation were evaluated in rat bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.


RESULTS
In comparison with untreated tumors, we noted a significantly decreased microvessel density (MVD) in the rat bladder cancer treated by TNP-470, and a significantly increased apoptotic index (AI) when treated by cisplatin. In TNP-470 plus cisplatin-treated tumors, both significantly decreased MVD and increased AI were observed in non-invasive and invasive rat bladder cancers in addition to a significantly decreased proliferation index (PI) in invasive cancer.


CONCLUSIONS
The combination therapy of TNP-470 with cisplatin may act through both the inhibition of angiogenesis and induction of apoptosis, and invasive tumor cells may be much more sensitive to this combined therapy in rat bladder cancer.
Zhang
Xianghua
X
Department of Urology, Kagawa Medical University, 1750-1 Miki-cho Kita-gun, Kagawa 761-0793, Japan. zhang@kms.ac.jp
Yamashita
Motoki
M
Uetsuki
Hirotsugu
H
Kakehi
Yoshiyuki
Y
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D003510:Cyclohexanes; D004273:DNA, Neoplasm / Q000032:analysis; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D008833:Microcirculation / Q000187:drug effects; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology
D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012717:Sesquiterpenes; D002945:Cisplatin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol