Dasatinib inhibits testosterone propionate-induced benign prostate hyperplasia in mice
10.3969/j.issn.1009-8291.2024.12.016
- VernacularTitle:达沙替尼可抑制丙酸睾酮诱导的小鼠前列腺增生
- Author:
Yue GU
1
;
Yiwei WANG
1
;
Bin XU
1
Author Information
1. Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
- Publication Type:Journal Article
- Keywords:
benign prostate hyperplasia;
dasatinib;
finasteride;
Ki-67;
testosterone propionate
- From:
Journal of Modern Urology
2024;29(12):1104-1109
- CountryChina
- Language:Chinese
-
Abstract:
[Objective] To analyze the therapeutic effects of dasatinib on testosterone propionate (TP)-induced benign prostatic hyperplasia (BPH) in animal experiments. [Methods] Institute of Cancer Research (ICR) mice were randomly divided into normal control group (n=5), BPH group (n=5), finasteride group (n=8), vehicle group (n=8), dasatinib intermittent administration group (n=10) and dasatinib continuous administration group (n=10). Except for the normal control group, BPH modelling was performed by subcutaneous injection of TP, and the groups were treated with saline, finasteride, polyethylene glycol 400 (PEG400) and dasatinib by gavage, respectively. The mice were sacrificed after a 14-day modelling period and a 28-day administration period. The prostate and spleen were dissected, and serum was sampled. Prostate weight was measured and prostate index (PI) was calculated. HE staining was conducted on the prostate and spleen, and Ki-67 immunohistochemical staining was performed on the prostate. Differences in the levels of serum dihydrotestosterone (DHT) and prostate-specific antigen (PSA) were detected with ELISA. [Results] The prostate weight and PI were significantly reduced in the dasatinib intermittent and continuous administration groups than in the BPH group (P<0.000 1), and the serum DHT level was also significantly reduced (P<0.01), but there were no significant differences in prostate weight, PI and serum DHT between dasatinib intermittent and continuous administration groups (P>0.05), and no significant difference in PSA level among the three groups (P>0.05). After dasatinib treatment, the pathological manifestations of prostate glandular and interstitial hyperplasia were significantly improved; the positive rate of Ki-67 was lower in the dasatinib intermittent and continuous administration groups than in the BPH group (P<0.001). [Conclusion] Dasatinib can inhibit TP-induced BPH, reduce serum DHT level, and inhibit the proliferation of prostate glandular and interstitial cells in mice. The therapeutic effects of intermittent administration of dasatinib are consistent with those of continuous administration.
