Inhibition of tumor angiogenesis during cisplatin chemotherapy for bladder cancer improves treatment outcome.
OBJECTIVE
To investigate the effect of inhibiting tumor angiogenesis during cisplatinum-(II)-diamine dichloride (cisplatin) chemotherapy of bladder cancer (BC) in a rat model.


METHODS
Bladder cancer was induced in 64 male rats using 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine in their water supply for 20 weeks. The animals were then divided randomly into four groups of 16 rats each: a control BC group (group 1); a BC group treated with cisplatin (0.25 mg/kg body weight) by intraperitoneal injection twice every week (group 2); a BC group treated with the antiangiogenic factor TNP-470 (30 mg/kg body weight) by intraperitoneal injection twice every week (group 3); and a BC group treated with cisplatin plus TNP-470 (group 4, treatment regimens as described). Per group, 4 rats were killed weekly after the start of treatment, for 4 weeks. BC was confirmed using histologic characteristics, and the treatment outcomes were determined by measuring tumor microvascular density and cell proliferation and apoptosis indexes (PI and AI, respectively).


RESULTS
All animals had confirmed BC. Both group 3 (TNP-470) and group 4 (cisplatin plus TNP-470) had significantly decreased microvascular density compared with group 1 (P <0.05). Although both the PI and AI were significantly different between group 4 (cisplatin plus TNP-470) and group 1 (control BC; P <0.05), neither the PI nor AI was significantly different between group 2 (cisplatin) and group 4 (cisplatin plus TNP-470; P >0.05).


CONCLUSIONS
TNP-470 in conjunction with cisplatin chemotherapy resulted in a decrease in the microvascular density of BC in a rat model. However, TNP-470 did not appear to have a significant impact on the cisplatin effect against BC as measured by apoptosis and cell proliferation.
Kong
Chuize
C
Department of Urology, No. 1 Hospital of China Medical University, Heping District, Shenyang, People's Republic of China. urokong@hotmail.com
Zhu
Yuyan
Y
Sun
Changcheng
C
Li
Zeliang
Z
Sun
Zhixi
Z
Zhang
Xianghua
X
Takanaka
Ikusama
I
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000139:chemically induced / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003510:Cyclohexanes; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D007274:Injections, Intraperitoneal; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011897:Random Allocation; D051381:Rats; D012717:Sesquiterpenes / Q000008:administration & dosage; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000139:chemically induced / Q000188:drug therapy*
D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D003510:Cyclohexanes; D012717:Sesquiterpenes; D002945:Cisplatin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol