The Preliminary Study On The Effection Of Androgen On Established Of Mice Xenograft Models For Human Prostate Carcinoma

Objective:Observe the change of serum testosterone levels between the male immunodeficiency mice embedded different dose of testosterone pellets subcutaneously, explore the dose of testosterone that conform to the aging adult human males, as well as the impaction to the growth and important organ of the mice under different dose of testosterone.Methods:The research objection were76patients of The second hospital of Tianjin medical university from October2011to March2013, including56cases of50-80years old male patients without androgen therapy, and20cases with prostate cancer after castration, Elisa method to detect the serum testosterone level.64male SCID mice were randomly divided into experimental group and the control group, experimental group mice were embedded subcutaneously5mg,12.5mg, and20mg testosterone pellets, respectively. To observe the growth of the mice under the different doses of testosterone pellets, and detect the level of the mice’serum testosterone in postoperative2weeks and1,2,3months, determine the dose of testosterone conformed to the testosterone levels of the aging adult human males. Executed the mice after three months, took out prostate, testicles and liver to made HE staining on paraffin sections, observe the changes of the mice tissues morphology. To observe the change in the mice’ sperm production function under the different doses of testosterone.Analyses were performed using SPSS18.0. Normal distribution quantitative variables were presented as the mean±standard deviation (SD). An independent samples t-test were used to compare the data between two groups. P values<0.05were considered statistically significant.Results:1. The levels of the testosterone in56cases of50-80years old male patients without androgen therapy:3.7---10.3ng/ml, in20patients with prostate cancer after castration:0.8---1.9ng/ml.2. The variation of intact SCID male mice testosterone in the control group for3months during observation period was larger, significantly lower than the average level in the aging adult patients serum levels; And the variation of castrated SCID male mice’ testosterone was small, the average serum levels below the castrated male patients. The difference is statistically significant. In the experimental group, after3months observation period, the testosterone levels of intact SCID male mice changed amplitude; The serum testosterone levels of castrated SCID male mice embedded12.5mg testosterone subcutaneously were in accordance with the aging adult human males testosterone levels.3.Whether in castrated or intact mice can appear hyperplasia of prostate after subcutaneous embedding more than physiological doses of testosterone, under high dose (20mg), glands appear under local erosion, necrosis and mild atypia. Low dose of testosterone (5mg) does not affect the mice testicular sperm production function, the number and the activity of sperm, there was no significant difference between two groups, when given middle dose (12.5mg), the occurrence of sperm significantly suppressed. And given high dose of20mg, the occurrence of sperm and can maintain the normal levels. There was no significant difference of the sperm quantity and activity between the experimental group and the control group. Sizes of fat vacuoles can be founded in the cytoplasm of liver cell of castrated mice’s liver HE staining,inact group and androgen supplement group mice liver fat vacuoles were lower than castrated group,patt of no fat vacuoles.Conclusions:As the human prostate cancer xenograft host, the testosterone levels of castrated mice is more stability than intact mice. The serum testosterone levels were in accordance with middle and old aged males serum testosterone levels in the castrated mice embedded12.5mg testosterone subcutaneously, and the survival of those mice were in good condition, we use12.5mg androgen established human prostate cancer xenograft model of renal capsule in mice,and achieved high tumor take rates(>90%). Our study procides an experimental basis for building human prostate cancer in mice xenograft models.