Sorafenib's inhibition of prostate cancer growth in transgenic adenocarcinoma mouse prostate mice and its differential effects on endothelial and pericyte growth during tumor angiogenesis.
OBJECTIVE
To evaluate Sorafenib's efficacy (60 mg/kg/d per os) in preventing the transformation of high grade prostate intraepithelial neoplasia (HGPIN) into adenocarcinoma (ADC) and in inhibiting the onset and progression of poorly differentiated carcinoma (PDC) in transgenic adenocarcinoma mouse prostate (TRAMP) mice.


METHODS
Forty-four TRAMP mice were randomly divided into 2 groups of 22 and assigned to daily treatment by gavage with vehicle only or Sorafenib from the 10th to the 26th week of age. At 26 weeks of age the mice were killed, and their genitourinary apparatus was removed and examined by histology, immunohistochemistry and confocal microscopy.


RESULTS
Sorafenib reduced HGPIN growth and progression to ADC and was probably also effective in PDC inhibition. The major effect of Sorafenib was on tumor angiogenesis. Interestingly a dissociation between endothelial cells and pericytes was noted in treated PDC since inhibition of pericyte recruitment was less complete than that of endothelial cells.


CONCLUSIONS
Sorafenib's potent antiangiogenic action may be supposed to be exerted primarily by inhibiting endothelial proliferation and sprouting, whereas its inhibition of pericyte recruitment and maturation is less complete. These observations suggest that Sorafenib's effects could be improved by the joint employment of substances capable of interfering with the recruitment and organization of pericytes.
Bono
Aldo V
AV
Department of Urology, University of Brescia, Brescia, Italy.
Pannellini
Tania
T
Liberatore
Marcella
M
Montironi
Rodolfo
R
Cunico
Sergio Cosciani
SC
Cheng
Liang
L
Sasso
Francesco
F
Musiani
Piero
P
Iezzi
Manuela
M
D000230:Adenocarcinoma / Q000098:blood supply* / Q000473:pathology / Q000517:prevention & control; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001557:Benzenesulfonates / Q000494:pharmacology*; D018450:Disease Progression; D004354:Drug Screening Assays, Antitumor; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D019085:Fluorescent Antibody Technique, Direct; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D009536:Niacinamide / Q000031:analogs & derivatives; D020286:Pericytes / Q000187:drug effects* / Q000473:pathology; D010671:Phenylurea Compounds; D019048:Prostatic Intraepithelial Neoplasia / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000517:prevention & control; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib