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 h ormone-resistant prostate cancer cell lines after subcutaneous implantation in mice. However, subcutaneous xenograft models may not mimic human condit ions due to the absence of prostatic stromal cells at the ectopic site. The refore, we investigated the influence of linomide on local tumor growth and metastasis of the human hormone-resistant prostate cancer cell line PC-3 i n 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 mic e) received linomide 100 mg/kg/day in the drinking water (per os). The othe r 15 mice (group 2) served as controls. All mice were sacrified after 38 da ys followed by macroscopical and histological evaluation of local tumor gro wth and metastasis. Microvessel density was determined by immunohistochemic al staining for von Willebrand factor as well as silver staining followed b y 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 (39 5- 1,261 mg). The mean transversal diameter of the lymph node metastases wa s 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 (232-1,1 31 mg) and a mean lymph node metastasis diameter of 4.6 mm (1.3-5.9 mm). Mi crovessel density of the local tumor in the control and treatment group did not differ significantly. Conclusion: Contrary to the results reported in subcutaneous animal models, linomide per os has no effect on net tumor growth and metastasis after ort hotopic implantation of the human hormone-resistant prostate cancer cell li ne PC-3 in nude mice. Copyright (C) 2000 S. Karger AG, Basel.