前列腺增生组织中bFGFmRNA表达的意义

目的 探讨前列腺组织中碱性成纤维细胞生长因子（ｂＦＧＦ）基因和蛋白及基受体表达的意义。方法 应用原位分子杂交和免疫组化方法检测３８例前列腺增生（ＢＰＨ）组织和１０例正常前列腺（ＮＰ）组织中ｂＦＧＦｍＲＮＡ、ｂＦＧＦ和ＦＧＦＲ１表达。结果 前列腺间质细胞和上皮细胞中均见ｂＦＧＦｍＲＮＡ、ｂＦＧＦ和ＦＧＦＲ１阳性染色。ＢＰＨ间质细胞中三者表达显著高于ＮＰ组织,但ＢＰＨ与ＮＰ上皮细胞中三者表达无显著性。     

前列腺组织中EGF、bFGF的表达

目的：研究EGF、bFGF在前列腺组织中的表达。方法：应用mRNA斑点杂交、原位杂交、免疫组织化学及原位杂交与免疫组织化学双染法检测6例正常前列腺（NP）、27例良性前列腺增生症（BPH）前列腺组织中EGF及bFGF的表达。结果：BPH前列腺组织和NP组织中无均无EGF mRNA表达,EGF蛋白表达呈弱阳性,两组间差异无显著性意义（P＞0.05）;NP组织上皮细胞有较多bFGF mRNA表达,但无bFGF翻译,基底基质细胞有少量mRNA及蛋白表达,二者表达水平基本一致;BPH前列腺组织上皮细胞无bFGF mRNA表达,但局灶性增殖上皮细胞细胞膜上有bFGF,基底基质细胞有大量bFGF mRNA转录及蛋白质翻译,以局灶性增殖区最为明显。结论：NP及BPH的前列腺组织中无EGF分泌细胞;bFGF在前列腺基底基质细胞过度表达,以自分泌、旁分泌方式促进了基质和上皮的非均一性增殖。     

Possible autocrine loop of the epidermal growth factor system in patients with benign prostatic hyperplasia treated with finasteride: a placebo-controlled randomized study

OBJECTIVE: To analyse the expression of the epidermal growth factor (EGF) system in prostate tissue and secretions obtained from patients with benign prostatic hyperplasia (BPH) treated with or without finasteride (which primarily targets the androgen-sensitive secretory epithelial cells in the prostate, with little effect on basal epithelial and stromal cells). PATIENTS AND METHODS: The expression of the EGF system was evaluated by enzyme-linked immunosorbent assay and immunohistochemistry in samples of prostate tissue and secretions from patients with BPH randomized for treatment with finasteride or placebo for 3 months before surgery. RESULTS: Prostate tissue expressed the EGF receptor (HER1) and HER2, and the ligands EGF, transforming growth factor alpha (TGFalpha), heparin-binding (HB) EGF, betacellulin and amphiregulin. Treatment with finasteride produced greater concentrations of amphiregulin (P < 0.05) than did placebo, did not change the level of TGFalpha, HER1 and HER2, and tended to decrease the concentration of EGF, betacellulin and HB-EGF in prostate tissue. Using immunohistochemistry, HER1 and TGFalpha were both localized to the basal epithelial cells, and there was a strong positive correlation among the tissue concentrations of HER1, HER2 and TGFalpha. Amphiregulin localized to the luminal secretory epithelium. Prostate secretions contained only EGF, which was at levels approximately 150 times higher than in prostate tissue; treatment with finasteride did not affect the concentration of EGF in prostate secretion. CONCLUSIONS: There were only minor changes in the expression of TGFalpha, HER1 and HER2 after finasteride treatment. This may represent an important system for the continuous growth and homeostasis of the androgen-independent basal epithelial cells in the prostate.     

Alpha 1-adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia.

PURPOSE: Recent evidence indicated that an alpha 1 blocker, doxazosin, induces prostate apoptosis in patients with benign prostatic hyperplasia (BPH). In this study, to determine whether this apoptotic response was mediated by alpha 1 adrenoceptor-dependent mechanism or was specific to doxazosin, we examined the effect of another alpha 1 blocker, terazosin, in addition to doxazosin, on the dynamics of prostate cell growth. MATERIALS AND METHODS: Cell proliferation and apoptosis were evaluated in BPH patients, an untreated (control) group (n = 31), and men treated with terazosin (n = 42) and doxazosin (n = 61) for the relief of the obstructive symptoms. Terazosin (1 to 10 mg./day) and doxazosin (2 to 8 mg./day) treatment varied from 1 week to 3 years. Ki-67 immunostaining and the TUNEL assay were used to evaluate the proliferative and apoptotic indices, respectively, in both the epithelial and stromal components of prostate (biopsy and prostatectomy) specimens. The smooth muscle cell content of the prostatic stroma was identified on the basis of smooth muscle alpha-actin immunoreactivity. RESULTS: A significant induction of apoptosis was observed in both the prostatic epithelial and stromal cells within the first month of terazosin and doxazosin therapy, as compared with untreated controls (p < 0.05). Furthermore, the marked induction of prostatic stroma apoptosis in response to both alpha 1 adrenoceptor antagonists was paralleled by a significant decrease in the smooth muscle alpha-actin expression. This loss of prostatic smooth muscle cells correlated with morphological stromal regression (as detected by trichrome staining) and BPH symptom improvement. Neither terazosin nor doxazosin therapy resulted in significant changes in prostate cell proliferation. CONCLUSIONS: These findings demonstrate that alpha-blockers as a class may regulate prostate growth by inducing apoptosis in both the epithelial and stromal cells, with little effect on cell proliferation. Apoptosis-mediated prostate stromal regression appears as a molecular mechanism underlying the therapeutic response to alpha 1 blockade in the treatment of BPH.     

Combined effect of terazosin and finasteride on apoptosis, cell proliferation, and transforming growth factor-beta expression in benign prostatic hyperplasia

BACKGROUND: Medical treatment of benign prostatic hyperplasia (BPH) targets relief of symptoms by causing either relaxation of the prostatic smooth muscle with alpha1 adrenergic blockade, or shrinkage of the gland with 5alpha-reductase inhibitors. We recently demonstrated that alpha1-blockers, such as terazosin, induce apoptosis in prostatic cells. In this study, we examined the combined effect of finasteride and terazosin on the rate of apoptosis and cellular proliferation to investigate their potential synergy at the cellular level. METHODS: Prostate specimens were obtained from men who were treated with either finasteride (n = 24), terazosin (n = 42), or combination therapy (n = 10) for varying time periods (1 week to 36 months) for the relief of the symptoms of BPH. The proliferative and apoptotic indices of both stromal and epithelial prostatic cell populations were determined. Antibodies against TGF-beta1 and TbetaRII were used to examine the immunoreactivity of TGF-beta1 and TbetaRII, respectively, in all prostate tissue sections. RESULTS: The apoptotic index in both prostate cell populations was significantly higher following the combination treatment compared to terazosin or finasteride alone. There were no significant changes in the rate of cellular proliferation with any treatment. Furthermore, there was a significant increase in TGF-beta1 expression in the prostates of patients treated with terazosin or combination therapy, while there was no change in TbetaRII expression. CONCLUSIONS: These results support the concept that induction of prostate apoptosis is a potential molecular mechanism underlying the combination effect of alpha1 blockade with 5alpha-reductase inhibitors in the effective treatment of BPH. The upregulation of TGF-beta1 implies a role for this ligand as an effector of apoptosis induction in response to alpha1-blockade or finasteride therapy of BPH patients.     

Effect of β radiation on TGF-β1 and bFGF expression in hyperplastic prostatic tissues

AIM: To investigate the transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) expressions in benign prostatic hyperplasia (BPH) and the effect of beta-radiation. METHODS: TGF-beta1 and bFGF expression was studied by means of an immunohistochemical method in nine normal prostatic (NP) tissues, 15 hyperplastic prostatic tissues and 35 hyperplastic prostatic tissues treated with 90Sr/90Y. RESULTS: The TGF-beta1 expression in the epithelium and stroma of normal prostatic tissues was 68.2 % +/- 10.5 % and 29.7 % +/- 4.6 %, respectively, while it was 64.8 % +/- 9.3 % and 28.6 % +/- 4.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, TGF-beta1 expression in the epithelia and stroma of BPH treated with 90Sr/90Y increased significantly (P <0.01). The bFGF expression in epithelia and stroma of normal prostatic tissues was 17.4 % +/- 3.7 % and 42.5 % +/- 6.8 %, respectively, and was 46.3 % +/- 8.2 % and 73.2 % +/- 12.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, expressions of bFGF in the epithelia and stroma of BPH treated with a 90Sr/90Y prostatic hyperplasia applicator decreased significantly (P <0.01). CONCLUSION: Exposure of beta-rays had noticeable effects on BPH tissues, enhancing TGF-beta1 expression and inhibiting bFGF expression.     

Decreased suburethral prostatic microvessel density in finasteride treated prostates: a possible mechanism for reduced bleeding in benign prostatic hyperplasia

PURPOSE: We evaluated the influence of finasteride on prostatic microvessel density to elucidate a mechanism of decreased bleeding in finasteride treated patients with hematuria secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 22 patients with clinical BPH and gross hematuria who underwent prostate reductive surgery between 1998 and 2000 were prospectively evaluated. The prostate from 10 finasteride treated and 12 untreated patients was immunohistochemically stained for CD-34. Microvessel density analysis was performed by quantifying positive stained blood vessels located within the stroma of hyperplastic nodules as well as in the suburethral portion of the prostate. RESULTS: Mean microvessel density plus or minus standard deviation in finasteride treated patients was significantly lower in the suburethral portion of the prostate versus untreated controls (14.0 +/- 2.8 versus 20.2 +/- 5.3 vessels per high power field, p <0.05). In the nodular hyperplasia there was no statistically significant difference in the treatment and control groups (mean 17.5 +/- 2.8 and 16.7 +/- 4.6 vessels per high power field, respectively). CONCLUSIONS: Finasteride significantly decreases suburethral prostatic microvessel density in patients with BPH, which may explain its efficacy for decreasing BPH associated bleeding.     

INDUCTION OF PROSTATE APOPTOSIS BY DOXAZOSIN IN BENIGN PROSTATIC HYPERPLASIA

Purpose

The molecular mechanisms underlying the therapeutic effect of the alpha 1 blocker, doxazosin, on benign prostatic hyperplasia (BPH) are poorly understood. We evaluated the effect of doxazosin on cell proliferation and apoptosis in the prostatic glandular epithelium and stroma of patients with BPH.

Materials and Methods

We examined proliferative and apoptotic activities in prostate specimens of 22 men a mean of 65 years old with BPH before and after doxazosin treatment within the normal therapeutic range. Proliferative and apoptotic indexes were determined using Ki-67 nuclear antigen staining and the terminal transferase end labeling assay, respectively. The smooth muscle cell content in prostatic specimens was identified by smooth muscle alpha-actin, and desmin immunoreactivity and apoptotic indexes were correlated with prostatic stromal tissue regression and improvement in BPH symptoms.

Results

In response to doxazosin treatment there were no significant changes in the kinetics of cell proliferation in the prostatic epithelial or stromal cell population. Mean pretreatment baseline apoptosis was 1.9 and 1.0% for the epithelial and stromal prostate components, respectively. Mean apoptotic indexes significantly increased after 3 months of doxazosin treatment in the glandular epithelial (6%) and smooth muscle cells (15%). By 12 months after treatment epithelial apoptosis had decreased to constitutive levels, while the apoptotic index of prostatic stroma cells remained high. Doxazosin induced smooth muscle cell apoptosis correlated with prostatic stromal degeneration, decreased alpha-smooth muscle actin expression and improved BPH symptoms.

Conclusions

These findings implicate the induction of prostate apoptosis by doxazosin as a potential molecular mechanism underlying the acute and chronic therapeutic responses of BPH to alpha 1 blockade.     

Benign prostatic hyperplasia and growth factors.

A great deal of work has been accomplished in the attempt to determine the cause of benign prostatic hyperplasia (BPH). Early work by morphologists suggests that BPH starts as a stromal disease and that the hyperplastic stroma secretes a substance that stimulates the growth of epithelial cells. The quantitative morphometric data also suggest that BPH is primarily a stromal disease. Experimental embryology data have shown that the basic fibroblast growth factor, bFGF, is involved in early embryogenesis and is the primary inducer of mesodermal tissue. Work in mouse embryos has shown that a powerful inducer for prostatic epithelial growth is elaborated by the urogenital mesenchyme. Both of these findings fit the hypothesis that stromal hyperplasia may be initiated by a growth factor and that a second growth factor stimulates epithelial growth. Work in our laboratory has established that bFGF is the primary growth factor present in human BPH. We have also found that bFGF is synthesized by prostate fibroblasts and bFGF may be in higher concentration in the periurethral tissues of BPH. At this time, no definite link between growth factors and hyperplastic growth of the prostate has been established. However, circumstantial evidence has lead us to formulate several hypothesis regarding the role of growth factors in BPH. Hopefully, these hypothesis will be of some assistance in guiding future work on growth factors and BPH.     

Apoptotic and proliferative index after Alpha-1-adrenoceptor antagonist and/or finasteride treatment in benign prostatic hyperplasia

INTRODUCTION: The induction of apoptosis has emerged as a potential target for optimization of the medical management of benign prostatic hyperplasia (BPH), recently. The influence of alpha1-adrenoceptor antagonist (alpha1-ARA), 5-alpha reductase inhibitor and their combination on prostatic cell apoptotic and proliferative indices of benign hyperplastic prostate gland were investigated. MATERIALS AND METHODS: A total of 49 male patients with BPH (mean age: 66.5 years) treated with alpha1-ARA and/or finasteride were retrospectively evaluated. Patients treated with alpha1-ARA (doxazosin n = 12 and terazosin n = 10), finasteride (n = 9) and combination of finasteride and alpha1-ARA (n = 9) were enrolled in the study. Primary antibodies were Ki-67 and proliferating cell nuclear antigen for the evaluation of proliferation in prostate stromal and epithelial cells. In situ apoptotic DNA fragmentation was evaluated using TUNEL assay. RESULTS: All treatment groups had no significant changes in the rate of prostate stromal and epithelial cell proliferation. Epithelial apoptotic index (AI) was not statistically significant for finasteride vs. alpha1- ARA, alpha1-ARA vs. finasteride + alpha1-ARA and finasteride + alpha1-ARA vs. finasteride groups. While alpha1-ARA was more effective than finasteride on stromal apoptosis, alpha1-ARA-induced stromal apoptosis was not significantly different from alpha1-ARA plus finasteirde treatment. CONCLUSION: Not only androgen variabilities but also alterations in sympathetic neurotransmission with age could have important implications for pathophysiological prostate growth. The combination of finasteride and alpha1-ARA is not superior to alpha1-ARA therapy with their similar epithelial and stromal apoptotic effects with unaffected cell proliferation.     

Expression of survivin and apoptotic biomarkers in benign prostatic hyperplasia

PURPOSE: We assessed the differential expression of survivin and other apoptotic markers in stromal and epithelial compartments of benign prostatic hyperplasia (BPH) and normal prostate tissue. MATERIALS AND METHODS: Immunohistochemical staining for survivin, and transforming growth factor-beta1 and its receptors was done in normal prostate and BPH areas from 114 consecutive patients who underwent radical prostatectomy. Moreover, staining for survivin, Bcl-2, Bax, caspase-3 and Ki-67 was performed in prostate specimens from 23 consecutive patients who underwent open prostatectomy and 4 young patients who underwent cystoprostatectomy and had a normal prostate. RESULTS: Survivin and Bcl-2 expression increased incrementally from normal prostate to epithelial BPH to stromal BPH. Caspase-3 expression was higher in BPH epithelium than in BPH stroma, which in turn was higher than that in normal prostate. Ki-67 was significantly over expressed in BPH stroma and epithelium. Survivin expression in BPH tissue correlated with International Prostate Symptom Score, quality of life, post-void residual urine volume, maximum urine flow rate and transforming growth factor-beta1 expression. CONCLUSIONS: Survivin is over expressed in BPH and it correlates with BPH parameters. Increases in proliferation and inhibition of apoptosis have a role in BPH.     

Interleukin-8 expression is increased in senescent prostatic epithelial cells and promotes the development of benign prostatic hyperplasia

BACKGROUND: Benign prostatic hyperplasia (BPH) is an extremely common disease of older men characterized by increased growth of prostatic epithelial and stromal cells. Previously we showed that senescent epithelial cells accumulate in the prostate of aging men and secrete interleukin-1 alpha (IL-1 alpha). IL-8 is also present at increased levels in BPH tissues and induces expression of FGF2, a potent stromal growth factor. Therefore, we sought to determine if IL-8 is also expressed at increased levels by senescent epithelial cells and if this secreted IL-8 plays a role in the pathogenesis of BPH. METHODS: Expression of IL-8 in human BPH tissue and primary cultures of prostatic epithelial cells was analyzed using an enzyme-linked immunoabsorption assay (ELISA). Tissue senescence was assessed by a quantitative assay for senescence-associated beta galactosidase (SA-beta gal). Proliferation of primary and immortalized prostatic epithelial cells in response to IL-8 was determined by counting of cells at intervals after addition of IL-8. RESULTS: Expression of IL-8 is significantly increased in vitro when cultured prostatic epithelial cells undergo senescence. Quantitative assay of BPH tissue extracts revealed that tissue IL-8 levels are correlated with both SA-beta gal activity and prostate weight. IL-8 promotes proliferation of primary and immortalized prostatic epithelial cells in culture. CONCLUSIONS: Senescence of prostatic epithelial cells results in increased expression of IL-8, which can promote proliferation of non-senescent epithelial and stromal cells by direct and indirect mechanisms, and in this manner contributes to the increased tissue growth seen in BPH.     

前列腺增生和癌变组织中碱性成纤维细胞生长因子的表达及其临床意义

为了探讨碱性成纤维细胞生长因子（ｂＦＧＦ）在前列腺组织中表达、分布情况及临床意义，应用免疫组化方法检测１４例正常前列腺（ＮＰ）、５６例前列腺增生症（ＢＰＨ）和３３例前列腺癌（Ｐｃａ）组织中ｂＦＧＦ的分布和表达。结果显示：ＢＰＨ中ｂＦＧＦ阳性率为６４３％，主要分布于间质细胞核，部分间质细胞浆、少数腺上皮细胞浆也见阳性染色；Ｐｃａ中ｂＦＧＦ阳性表达位于癌细胞浆，阳性率为８４８％，但ｂＦＧＦ表达强度与Ｐｃａ的病理分级、临床分期无明显关系；正常前列腺组织中ｂＦＧＦ表达均为阴性，三者之间阳性率差异有显著意义，表明ｂＦＧＦ参与ＢＰＨ、Ｐｃａ发生过程。     

Selectivity of finasteride as an in vivo inhibitor of 5alpha-reductase isozyme enzymatic activity in the human prostate

The type II 5alpha-reductase inhibitor finasteride is used in the treatment of benign prostatic hyperplasia (BPH), reducing local production of the growth promoting androgen dihydrotestosterone (DHT). The effect of prolonged treatment with this time-dependent irreversible inhibitor on the recently described prostatic type I 5alpha-reductase, however, is not clear. Therefore, we assessed the effects of 5 mg. finasteride per day for 6 months on prostatic 5alpha-reductase isozymes, and prostatic tissue composition and androgen content of patients suffering from BPH. In prostatic tissue from these patients, the type II enzymatic activity is inhibited 100-fold compared with tissues obtained from placebo treated patients. The type II immunoreactivity is up regulated 2-fold. The type I isozyme is inhibited 3-fold and potentially still contributes to DHT production. In conclusion, finasteride is a selective type II inhibitor in vivo. Further research is warranted to assess the possibly distinct roles of the 5alpha-reductase isozymes in the normal prostate, in BPH, and during finasteride treatment.     

Does long-term finasteride therapy affect the histologic features of benign prostatic tissue and prostate cancer on needle biopsy? PLESS Study Group. Proscar Long-Term Efficacy and Safety Study

OBJECTIVES: Finasteride, a common agent used to treat benign prostatic hyperplasia (BPH), inhibits 5-alpha-reductase. Testosterone is converted by 5-alpha-reductase to the more potent dihydrotestosterone, which is the primary androgen in the prostate. Leuprolide is a stronger antiandrogen that is used to downstage prostate cancer before radical prostatectomy. Leuprolide induces marked atrophy of prostate carcinoma cells, which sometimes makes pathologic diagnosis of cancer difficult, although evaluation at radical prostatectomy is easier than at biopsy. It is unknown whether finasteride produces similar changes, which would result in greater diagnostic difficulty because such changes would be seen on biopsy to rule out cancer in men with suspicious clinical findings treated for BPH. The current study investigated the histologic effects of finasteride therapy on human prostate cancer and benign prostatic tissue on needle biopsy. METHODS: In blinded manner, we reviewed 53 needle biopsy specimens showing prostate carcinoma (35 treated with finasteride, 18 with placebo). Also reviewed in blinded manner were 50 benign needle biopsy specimens (25 treated with finasteride, 25 with placebo). The Gleason score, number of cores involved, percentage cancer involvement in a core, percentage of atrophic changes in cancer cells, presence of mitoses, blue-tinged mucinous secretions, prominent nucleoli, and high-grade prostatic intraepithelial neoplasia were documented for each case in the cancer group. The percentage of atrophy, basal cell hyperplasia, transitional metaplasia, chronic inflammation, and stromal proliferation was documented for each case in the benign group. RESULTS: No significant histologic differences were present in either the benign or cancer group between cases treated with finasteride and placebo. CONCLUSIONS: We conclude that finasteride treatment for BPH does not cause difficulty in the diagnosis of cancer in prostate needle specimens. It is possible that there are severely atrophic areas resulting from finasteride treatment that are undersampled. However, the conclusion that cancer seen on needle biopsy in men treated with finasteride is unaltered and readily identified as cancer remains valid.     

Expression of p75(LNGFR) and Trk neurotrophin receptors in normal and neoplastic human prostate.

OBJECTIVE: To analyse the occurrence and cell distribution of p75(LNGFR) and Trk neurotrophin receptors in normal prostate, benign prostatic hypertrophy (BPH) and prostate carcinoma, and to determine the effect of androgen suppression on the expression of these proteins in prostate cancer samples. MATERIALS AND METHODS: The study comprised formalin-fixed and paraffin-embedded material, obtained during surgery and from cadavers during removal of organs for transplantation. Light microscopy immunohistochemistry was carried out using polyclonal antibodies against Trks, and a monoclonal antibody against p75(LNGFR). General markers for epithelial and endocrine cells were assessed in parallel. RESULTS: TrkA immunoreactivity (IR) was restricted to the basal epithelial cells in some acini (37%). This pattern remained unchanged or IR extended to the whole acini in BPH, and varied widely in prostate cancer. In normal tissue and BPH, TrkC IR was detected exclusively in the stroma. Nevertheless, it progressively increased in the epithelial cells of well-differentiated to moderately differentiated prostate carcinoma, whereas in stromal cells there were no substantial changes. TrkB IR was absent in all the samples. There was weak p75(LNGFR) IR in normal epithelial cells, which increased in prostate cancer and to a lesser extent in BPH. Androgen suppression was ineffective in reversing TrkA modifications, whereas it caused a decrease in the expression of TrkC and p75(LNGFR). CONCLUSION: The abnormal growth of prostatic epithelium is accompanied by increased TrkA expression and the induction of TrkC expression in epithelial cells. These results suggest that neurotrophins could be involved in the abnormal growth of the human prostate, acting through specific Trk signal-transducing receptors whose expression is regulated by androgens.     

bFGF和TGF-β1对原代培养的前列腺间质细胞的作用

目的:探讨碱性成纤维细胞生长因子(bFGF)和转化生长因子β1(TGF-β1)在良性前列腺增生(BPH)中的作用。方法:培养了人BPH间质细胞,采用MTT法检测无血清培养的间质细胞的增殖,用免疫组化方法检测平滑肌细胞表型变化,观察不同浓度bFGF和TGF-β1对培养的人BPH间质细胞的影响。结果:bFGF促进间质细胞增殖(P<0.05、P<0.01),较高浓度时(10μg/L)降低平滑肌细胞表型表达;TGF-β1(>0.1μg/L)抑制间质细胞增殖并增加平滑肌细胞表型表达(P<0.05、P<0.01);5μg/L的bFGF与0.001μg/L和0.01μg/L TGF-β1作用间质细胞,促进细胞增殖(P<0.01),与0.1μg/L,1μg/L及10μg/L TGF-β1作用间质细胞,抑制细胞增殖,0.1μg/L时对细胞的抑制作用轻微(P>0.05),1μg/L及10μg/L时出现明显的抑制(P<0.01),同时TGF-β1在较高浓度时(>1μg/L),平滑肌细胞表型表达明显增加(P<0.01)。结论:bFGF以时间和浓度依赖的方式促进培养的增生前列腺间质细胞的增殖,并减少平滑肌细胞表型表达;TGF-β1抑制间质细胞的生长并诱导间质细胞向平滑肌细胞分化,两者共同在BPH的形成机制中发挥着重要作用。