Influence of linomide on local tumor growth and metastasis of the human hormone-resistant prostate cancer cell line PC3 in an orthotopic model.
OBJECTIVE
It has been demonstrated that quinoline-3-carboxamide, linomide, inhibited angiogenesis and reduced the volume of tumors grown from human hormone-resistant prostate cancer cell lines after subcutaneous implantation in mice. However, subcutaneous xenograft models may not mimic human conditions due to the absence of prostatic stromal cells at the ectopic site. Therefore, we investigated the influence of linomide on local tumor growth and metastasis of the human hormone-resistant prostate cancer cell line PC-3 in an orthotopic model.


METHODS
In 30 athymic nude mice, 5x10(5) PC-3 cells were injected into the dorsal prostate after surgical exposure. After 7 days, group 1 (n = 15 mice) received linomide 100 mg/kg/day in the drinking water (per os). The other 15 mice (group 2) served as controls. All mice were sacrificed after 38 days followed by macroscopical and histological evaluation of local tumor growth and metastasis. Microvessel density was determined by immunohistochemical staining for von Willebrand factor as well as silver staining followed by morphometric analysis in an area of highest vessel density.


RESULTS
In the control group, local tumorigenicity and locoregional lymph node metastasis was 100%. The mean weight of the local tumor was 894 mg (395- 1,261 mg). The mean transversal diameter of the lymph node metastases was 4.0 mm (1.5-5. 4 mm). In the treatment group, local tumor growth and lymph node metastasis was 100% with a mean local tumor weight of 869 mg (232-1, 131 mg) and a mean lymph node metastasis diameter of 4.6 mm (1.3-5.9 mm). Microvessel density of the local tumor in the control and treatment group did not differ significantly.


CONCLUSIONS
Contrary to the results reported in subcutaneous animal models, linomide per os has no effect on net tumor growth and metastasis after orthotopic implantation of the human hormone-resistant prostate cancer cell line PC-3 in nude mice.
Bex
A
A
Urologische Klinik und Poliklinik, Universitätsklinikum Essen, Germany.
Luboldt
H
H
Sudermann
T
T
Rembrink
K
K
Otto
T
T
Rübben
H
H
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D006912:Hydroxyquinolines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology*; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D006912:Hydroxyquinolines; C045282:roquinimex