Effect of sildenafil citrate on an orthotopic prostate cancer growth and metastasis model.
OBJECTIVE
We characterized the effects of sildenafil citrate on the growth and metastasis of human prostate cancer cells in nude mice.


METHODS
The androgen independent human prostate cancer cell line PC-3 was inoculated into the prostate of nude mice to produce orthotopic primary prostate cancers and metastases. Sildenafil citrate gavage was started on day 31 after tumor cell inoculation and given every other day 15 times (30 days). The 7 mice in the low dose group received 25 mg/kg body weight sildenafil citrate per gavage, while the 7 in the high dose group received 50 mg/kg body weight sildenafil citrate and the 9 in the control group received water. Autopsy was performed on day 75 to evaluate primary tumor growth and metastasis. Plasma cyclic guanosine monophosphate concentrations were measured after the single dose of 50 mg/kg sildenafil citrate in the mice.


RESULTS
Plasma cyclic guanosine monophosphate concentration increased 4-fold 1 hour after sildenafil citrate administration. The plasma concentration decreased rapidly and returned to normal after 8 hours. There was no significant difference in tumor weight between any of the 3 groups. The number of metastatic lymph nodes correlated significantly with primary tumor weight (p = 0.03) with a correlation coefficient of 0.454 but there was no significant correlation between the number of involved lymph nodes and sildenafil administration. Distant metastases were not significantly promoted by sildenafil administration.


CONCLUSIONS
Incontinuous oral administration of sildenafil citrate did not promote primary tumor growth and metastasis in an orthotopic prostate cancer model.
Qian
Chao-Nan
CN
Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI, USA.
Takahashi
Masayuki
M
Kahnoski
Richard  J
R
Teh
Bin Tean
BT
D000818:Animals; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000473:pathology*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D006152:Cyclic GMP