Qian Chao-Nan, Takahashi Masayuki, Kahnoski Richard J, Teh Bin Tean
Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI, USA.
J Urol. 2003 Sep;170(3):994-7. doi: 10.1097/01.ju.0000080321.99119.df.
We characterized the effects of sildenafil citrate on the growth and metastasis of human prostate cancer cells in nude mice.
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.
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.
Incontinuous oral administration of sildenafil citrate did not promote primary tumor growth and metastasis in an orthotopic prostate cancer model.
我们研究了枸橼酸西地那非对裸鼠体内人前列腺癌细胞生长和转移的影响。
将雄激素非依赖性人前列腺癌细胞系PC-3接种到裸鼠前列腺中，以产生原位原发性前列腺癌和转移灶。在肿瘤细胞接种后第31天开始进行枸橼酸西地那非灌胃，每隔一天给药1次，共给药15次（30天）。低剂量组的7只小鼠每次灌胃给予25mg/kg体重的枸橼酸西地那非，高剂量组的7只小鼠每次灌胃给予50mg/kg体重的枸橼酸西地那非，对照组的9只小鼠给予水。在第75天进行尸检，以评估原发性肿瘤的生长和转移情况。在小鼠单次给予50mg/kg体重的枸橼酸西地那非后，测量血浆环磷酸鸟苷浓度。
给予枸橼酸西地那非1小时后，血浆环磷酸鸟苷浓度增加了4倍。血浆浓度迅速下降，8小时后恢复正常。3组之间的肿瘤重量没有显著差异。转移淋巴结的数量与原发性肿瘤重量显著相关（p = 0.03），相关系数为0.454，但受累淋巴结数量与西地那非给药之间没有显著相关性。西地那非给药并未显著促进远处转移。
在原位前列腺癌模型中，间断口服枸橼酸西地那非不会促进原发性肿瘤的生长和转移。
