Comparative study of apoptotic antitumor effect between angiogenesis inhibitor AGM-1470 and MVAC chemotherapy on rat urinary bladder cancer.
OBJECTIVE
To investigate the antitumor apoptotic effect of AGM-1470 by comparing it to that induced by methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy, currently the standard chemotherapy for bladder cancer, in a rat bladder cancer model.


METHODS
A total of 45 six-week-old female rats were divided into 3 equal groups: those receiving AGM-1470 treatment; those receiving MVAC treatment, and controls. All rats were cystectomized to evaluate the therapeutic effect with regard to macroscopic tumor findings, hematoxylin and eosin pathology, apoptosis detection, and immunohistochemistry (IHC) for bcl-2.


RESULTS
Our experimental protocol succeeded in producing invasive bladder tumors in the majority of rats. Tumor volume was significantly reduced in the AGM-1470 and MVAC treatment groups compared with that in the control group. The apoptotic indices of tumor cells was significantly higher in the AGM-1470 and MVAC treatment groups than in the control group. IHC for bcl-2 demonstrated no statistical difference in expression among the groups. However, the apoptotic indices of high-level bcl-2 expression were significantly lower than the indices of low-level expression in the AGM-1470 group.


CONCLUSIONS
AGM-1470 and MVAC appear to exert a prominent mass reduction effect via tumor cell apoptosis in cases of invasive bladder tumor, although these therapies did not demonstrate any obvious modulation of bcl-2 protein expression status. Bcl-2 overexpression might be an obstacle to AGM-1470 therapy because of its significant inhibitory effect on apoptosis.
Sejima
Takehiro
T
Division of Urology, Department of Surgery, Tottori University Faculty of Medicine, Yonago, Japan. sejimatkcd@384.jp
Isoyama
Tadahiro
T
Miyagawa
Ikuo
I
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000627:therapeutic use*; D003510:Cyclohexanes; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression; D019254:Genes, bcl-2; D006965:Hyperplasia; D008727:Methotrexate / Q000627:therapeutic use*; D023421:Models, Animal; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010212:Papilloma / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D008727:Methotrexate