Cyclopamine functions as a suppressor of benign prostatic hyperplasia by inhibiting epithelial and stromal cell proliferation via suppression of the Hedgehog signaling pathway.

Stromal­epithelial interaction serves a pivotal role in normal prostate growth, as well as the onset of benign prostatic hyperplasia (BPH). The present study aimed to explore the role of cyclopamine in the proliferation and apoptosis of epithelial and stromal cells in rats with BPH by blocking the Hedgehog signaling pathway. Cyclopamine (an inhibitor of the Hedgehog signaling pathway) was administered in a rat model of BPH, and the expression of Ki67 (proliferation factor) was determined by immunohistochemistry. In addition, epithelial and stromal cells were separated and cultured in order to investigate the role of cyclopamine in the progression of BPH. The expression of Hedgehog signaling pathway­ and apoptosis­related genes, including basic fibroblastic growth factor (b­FGF) and transforming growth factor ß (TGF­ß), was evaluated using reverse transcription­quantitative polymerase chain reaction and western blot analysis. Cell proliferation, cell cycle and apoptosis were analyzed using an MTT assay and flow cytometry. We identified upregulated Ki67 expression and activated Hedgehog signaling pathway in rats with BPH. Cyclopamine inhibited the activation of the Hedgehog signaling pathway. In response to cyclopamine treatment, epithelial and stromal cell proliferation was inhibited; this was concomitant with decreased Ki67, TGF­ß, and b­FGF expression. On the other hand, epithelial cell apoptosis was enhanced, which was associated with increased Bax and reduced Bcl­2 expression. Based on these findings, we proposed that cyclopamine may serve as a potential therapeutic agent in the treatment of BPH. Cyclopamine could inhibit epithelial and stromal cell proliferation, and induce epithelial cell apoptosis by suppressing the Hedgehog signaling pathway.

[Qianlongtong capsule elevates the Smad4 gene expression in prostate stromal cells].

OBJECTIVE: To investigate the effects of the plasma containing Qianlongtong Capsule (QLT)-containing plasma on the expression of the Smad4 gene in prostate stromal cells in vitro and provide some experimental evidence for the treatment of benign prostatic hyperplasia (BPH) with Chinese medicinal compound. METHODS: Fifteen cases of BPH were equally randomized to three groups to be treated with QLT at a high dose (6 capsules once), a medium dose (3 capsules once), and a low dose (1.5 capsules once), tid, for 7 days consecutively. QLT-containing plasma was collected from the patients. Prostate stromal cells were identified by immunofluorescence when they became monolayered and cultured in the QLT-containing plasma for 24 hours, followed by detection of the expression of the Smad4 gene by real-time quantitative PCR and that of the Smad4 protein by Western blot. RESULTS: After treatment with the QLT-containing plasma, the expression of the Smad4 gene in the stromal cells was significantly increased in a dose-dependent manner as compared with the blank control and no-QLT groups (P < 0.01). The expression of the Smad4 protein was also markedly elevated after treatment. The differences were statistically significant between the blank control and medium-dose groups (P < 0.01), low-dose and medium-dose groups (P < 0.05), and high-dose and the other groups (P < 0.01), but not between the blank control and low-dose groups (P > 0.05). CONCLUSION: QLT-containing plasma could inhibit the proliferation and improve the apoptotic index of prostate stromal cells in vitro, which was related to the elevation of the mRNA and protein expressions of Smad4.

[Musk and carterii birdw enhance the effect of polygonum extract on chronic non-bacterial prostatitis: an animal experimental study].

OBJECTIVE: To observe the effects of musk and carterii birdw on the pathology and the expressions of inflammatory cytokines in chronic non-bacterial prostatitis (CNBP) rats treated with polygonum extract. METHODS: Five male Wistar rats were used for the preparation of SC purified prostate protein solution, and another 48 randomly divided into four groups: polygonum extract, polygonum extract + musk and carterii birdw, CNBP model control and normal control. CNBP models were established by injecting SC purified prostate protein solution and Freund's complete adjuvant. At 60 days after modeling, the CNBP model control and normal control rats were treated with normal saline, and the other two groups with polygonum extract and polygonum extract + musk and carterii birdw, respectively (polygonum 1.575 g per kg per d, musk 0.021 g per kg per d, and carterii birdw 1.05 g per kg per d). After 14 days of continuous intragastric medication, all the rats were sacrificed for pathological examination, determination of the levels of TNF-alpha, IL-1beta, IL-6 and IL-8 in the prostate tissue homogenate by ELISA, and detection of the mRNA and protein expressions of inflammatory cytokines MCP-1 (CCL2) and CCR2 by RT-PCR and Western blot. RESULTS: The polygonum extract + musk and carterii birdw group showed apparent improvement in the structure of the prostate tissue but no inflammatory infiltration, as was quite obvious in the polygonum extract group. Polygonum extract + musk and carterii birdw significantly decreased the inflammatory cytokines TNF-alpha ( [11.04 +/- 4.07] pg/ml), IL-1beta ([16.94 +/- 4.26] pg/ml), IL-6 ([110.08 +/- 28.42] pg/ml) and IL-8 ([26.28 +/- 7.36] pg/ml) in the prostate tissue, as compared with polygonum extract alone ([63.21 +/- 21.37] pg/ml, [41.32 +/- 14.62] pg/ml, [177.64 +/- 42.65] pg/ml and [96.37 +/- 37.61] pg/ml) (P < 0.05, P < 0.01). The former also exhibited significantly lower expressions of MCP-1 mRNA (0.32 +/- 0.17), MCP-1 protein (0.28 +/- 0.15), CCR2 mRNA (0.28 +/- 0.11) and CCR2 protein (0.11 +/- 0.04) than either the model control group (1.15 +/- 0.39, 0.93 +/- 0.34, 0.83 +/- 0.26 and 0.93 +/- 0.34) (P < 0.01), or the polygonum extract group (0.65 +/- 0.27, 0.56 +/- 0.22, 0.78 +/- 0.24 and 0.25 +/- 0.09) (P < 0.05, P < 0.01). CONCLUSION: Musk and carterii birdw can enhance the effect of polygonum extract on chronic prostatitis, reduce inflammatory response and improve tissue repair of the prostate in rats.

[Observation of the therapeutic effect of qianlie sanyu capsule on benign prostatic hyperplasia].

OBJECTIVE: To observe the clinical efficacy of Qianlie Sanyu Capsule on benign prostatic hyperplasia (BPH). METHODS: Seventy-two patients with BPH were randomly divided into a treatment group (40 patients) and a control group (32 patients), the former treated by Qianlie Sanyu Capsule and the latter by Longbishu. Observation were made on the changes of the patients' urination' symptoms, living quality, prostatic volume, Qmax uroflowmetry and excel urine before and after treatment. RESULTS: The total efficacy rates were 92.5% in the treatment group, and 72.5% in the control group. Comparison between the two groups showed significant difference (P < 0.01). The urination symptoms, living quality, Qmax uroflowmetry and the excel urine were better improved in the Qianlie Sanyu group than in the Longbishu. There were significant differences between the two groups (P < 0.05), but none in reducing effect on the prostatic volume. CONCLUSION: Qianlie Sanyu Capsule is an effective drug for BPH.