A novel mouse model simulating transurethral laser vaporization prostatectomy / 亚洲男科学杂志(英文版)

Benign prostatic hyperplasia (BPH) is a common disease in elderly men, and transurethral laser prostatectomy (TULP) has been widely used in the clinic to remove bladder outlet obstruction caused by BPH. Previous animal models for wound repair after prostatectomy have many limitations, and there have been no previous reports of a mouse model of TULP. Therefore, this study aimed to establish a novel mouse model of TULP. Twelve healthy adult Kunming (KM) mice received transurethral laser vaporization prostatectomy with a 200-μm thulium laser. The mice were sacrificed, and wound specimens from the prostatic urethra and bladder neck were harvested at 1 day, 3 days, 5 days, and 7 days after surgery. Hematoxylin-eosin (HE) and immunohistochemistry were applied to confirm the establishment of the mouse TULP model. One day after the surgery, urothelium expressing uroplakin (UPK) was absent in the urethral wound site, and a large number of necrotic tissues were found in the wound site. There was no UPK-positive urothelium in the wound 3 days after surgery. At 5 days after surgery, monolayer urothelium expressing UPK was found in the wound site, indicating that the re-epithelization of the wound had been completed. On the 7th day after surgery, there were multiple layers of urothelium with UPK expression, indicating that the repair was completed. It is feasible to establish a mouse TULP model by using a microcystoscope system and a 200-μm thulium laser.

Human umbilical cord Wharton's jelly-derived mesenchymal stem cell transplantation could improve diabetic intracavernosal pressure / 亚洲男科学杂志(英文版)

Mesenchymal stem cells (MSCs) secrete various cytokines with angiogenic and neuroprotective effects. This study aimed to assess the effects of human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on diabetes-related intracavernosal pressure (ICP) impairment in rats. hWJ-MSCs were isolated from human umbilical cord Wharton's jelly and transplanted into the corpus cavernosum of streptozotocin (STZ)-induced diabetic rats by unilateral injection. The erectile function was evaluated at 4 weeks, as well as the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS), and insulin-like growth factor 1 (IGF1). STZ-induced diabetic rats showed impaired ICP, which was significantly improved by hWJ-MSC treatment. VEGF, eNOS, IGF1, and bFGF expression levels were higher in hWJ-MSC injection sites than those in control ones in STZ-induced diabetic rats. These results suggest that hWJ-MSC transplantation might improve diabetic erectile dysfunction through increased production of paracrine growth factors, highlighting a novel potential therapeutic option for erectile dysfunction.

Prostatic anatomical parameters correlate with clinical characteristics suggestive of benign prostatic hyperplasia / 亚洲男科学杂志(英文版)

We conducted the present study to assess the correlation of the prostatic anatomical parameters, especially the ratio of peripheral zone thickness and transitional zone thickness, with clinical and uroflowmetry characteristics suggestive of benign prostate hyperplasia (BPH). A total of 468 consecutive patients with a detailed medical history were identified. All patients were evaluated by scoring subjective symptoms with the International Prostate Symptom Score (IPSS) and quality of life (QoL). The prostatic anatomical parameters were measured using transrectal ultrasonography, and postvoid residual urine and maximum flow rate (Q

Peripheral zone PSA density: a predominant variable to improve prostate cancer detection efficiency in men with PSA higher than 4 ng ml / 亚洲男科学杂志(英文版)

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml

Low-intensity pulsed ultrasound stimulates proliferation of stem/progenitor cells: what we need to know to translate basic science research into clinical applications / 亚洲男科学杂志(英文版)

Low-intensity pulsed ultrasound (LIPUS) is a promising therapy that has been increasingly explored in basic research and clinical applications. LIPUS is an appealing therapeutic option as it is a noninvasive treatment that has many advantages, including no risk of infection or tissue damage and no known adverse reactions. LIPUS has been shown to have many benefits including promotion of tissue healing, angiogenesis, and tissue regeneration; inhibition of inflammation and pain relief; and stimulation of cell proliferation and differentiation. The biophysical mechanisms of LIPUS remain unclear and the studies are ongoing. In recent years, more and more research has focused on the relationship between LIPUS and stem/progenitor cells. A comprehensive search of the PubMed and Embase databases to July 2020 was performed. LIPUS has many effects on stem cells. Studies show that LIPUS can stimulate stem cells in vitro; promote stem cell proliferation, differentiation, and migration; maintain stem cell activity; alleviate the problems of insufficient seed cell source, differentiation, and maturation; and circumvent the low efficiency of stem cell transplantation. The mechanisms involved in the effects of LIPUS are not fully understood, but the effects demonstrated in studies thus far have been favorable. Much additional research is needed before LIPUS can progress from basic science research to large-scale clinical dissemination and application.

Estradiol is an independent risk factor for organic erectile dysfunction in eugonadal young men / 亚洲男科学杂志(英文版)

Erectile dysfunction attributable to testosterone deficiency is less common in young males, and the effect of estradiol on erectile function in eugonadal young males is unclear. We analyzed data from 195 male participants, including 143 eugonadal patients with erectile dysfunction and 52 healthy men. To distinguish psychogenic and organic erectile dysfunction, penile rigidity was measured using the nocturnal penile tumescence rigidity test. Serum levels of sexual hormones were quantified by electrochemiluminescence, and penile vascular status was assessed by penile color Doppler ultrasound. Both serum estradiol levels and the ratio of estradiol to testosterone were higher in patients with organic erectile dysfunction than in patients with psychogenic erectile dysfunction or healthy controls. Organic erectile dysfunction was negatively associated with estradiol levels and the ratio of estradiol to testosterone, and estradiol was the only significant risk factor for organic erectile dysfunction (odds ratio: 1.094; 95% confidence interval: 1.042-1.149, P = 0.000). Moreover, serum estradiol levels were negatively correlated with penile rigidity. Serum estradiol levels were higher and penile rigidity was lower in patients with venous erectile dysfunction than in patients with nonvascular erectile dysfunction. We conclude that elevated serum estradiol levels may impair erectile function and may be involved in the pathogenesis of organic erectile dysfunction in eugonadal young men.

Comparison of diagnostic efficacy between transrectal and transperineal prostate biopsy: A propensity score-matched study / 亚洲男科学杂志(英文版)

This study compared the diagnostic efficacy of transrectal ultrasound (TRUS)-guided prostate biopsy (TRBx) and transperineal prostate biopsy (TPBx) in patients with suspected prostate cancer (PCa). We enrolled 2962 men who underwent transrectal (n = 1216) or transperineal (n = 1746) systematic 12-core prostate biopsy. Clinical data including age, prostate-specific antigen (PSA) level, and prostate volume (PV) were recorded. To minimize confounding, we performed propensity score-matching analysis. We measured and compared PCa detection rates between TRBx and TPBx, which were stratified by clinical characteristics and Gleason scores. The effects of clinical characteristics on PCa detection rate were assessed by logistic regression. For all patients, TPBx detected a higher proportion of clinically significant PCa (P < 0.001). Logistic regression analyses illustrated that PV had a smaller impact on PCa detection rate of TPBx compared with TRBx. Propensity score-matching analysis showed that the detection rates in TRBx were higher than those in TPBx for patients aged >- 80 years (80.4% vs 56.5%, P = 0.004) and with PSA level 20.1-100.0 ng ml-1 (80.8% vs 69.1%, P = 0.040). In conclusion, TPBx was associated with a higher detection rate of clinically significant PCa than TRBx was; however, because of the high detection rate at certain ages and PSA levels, biopsy approaches should be optimized according to patents' clinical characteristics.

Two-micron laser resection of the prostate-tangerine technique for the treatment of large-volume prostate / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficiency and safety of two-micron laser resection of the prostate-tangerine technique (TmLRP-TT) for the treatment of large-volume ( > 70 ml) prostate in patients with benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>This retrospective analysis included 80 BPH patients with the prostatic volume larger than 70 ml, all treated by TmLRP-TT. We comparatively analyzed the levels of hemoglobin and serum sodium before and after surgery, recorded intra- and post-operative com- plications, and followed up the patients at 6 and 12 months after operation for International Prostate Symptom Score (IPSS), quality of life (QOL), maximum flow rate (Qmax), and postvoid residual urine volume (PVR).</p><p><b>RESULTS</b>All the operations were successfully completed. The mean hemoglobin decreased (0.68 +/- 0.43) g/dl intraoperatively, but no apparent reduction was observed in serum sodium. Lower urinary tract symptoms were relieved significantly in all the cases. At 12 months after surgery, IPSS was decreased by 73.89% as compared with the baseline (20.03 +/- 6.9 vs 5.23 +/- 3.59), QOL by 64.55% (4.09 +/- 1.19 vs 1.45 +/- 1.36), and PVR by 79.30% (97.31 +/- 57.90 vs 20.14 +/- 24.20 ml), while Qmax increased by 140.42% ([8.04 +/- 3.62] vs [19.33 +/- 3.28] ml/s). The incidence of complications was low either intraoperatively or during the 12 months after operation.</p><p><b>CONCLUSION</b>TmLRP-TT is a safe and effective surgical endoscopic approach to the treatment of large-volume prostate in BPH patients.</p>

Novel role of microRNAs in prostate cancer / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To discuss the novel biomarkers of microRNAs in prostate cancer.</p><p><b>DATA SOURCES</b>The literatures about microRNAs and prostate cancer cited in this review were obtained mainly from Pubmed published in English from 2004 to 2012.</p><p><b>STUDY SELECTION</b>Original articles regarding the novel role of microRNAs in prostate cancer were selected.</p><p><b>RESULTS</b>MicroRNAs play an important role in prostate cancer such as cell differentiation, proliferation, apoptosis, and invasion. Especially microRNAs correlate with prostate cancer cell epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), drug sensitivity, cancer microenvironment, energy metabolism, androgen independence transformation, and diagnosis prediction.</p><p><b>CONCLUSIONS</b>MicroRNAs are involved in various aspects of prostate cancer biology. The role of microRNA in the initiation and development of prostate cancer deserves further study.</p>

Differential gene expressions in the stromal cells of the human prostate peripheral zone in males of different ages / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the gene expressions in the stromal cells of the human prostate peripheral zone (PZ) in men of different ages.</p><p><b>METHODS</b>We primarily cultured stromal cells from the normal prostate PZ of men aged 23 -32 (young group) and 56 -75 years (old group), profiled the gene signature of the PZ cells by cDNA microarray, and defined the differential gene expression patterns by hierarchical cluster analysis. Among the differential genes, we selected and confirmed up-regulated genes by quantitative real time PCR (Q-PCR), and identified their protein coding by Western blotting.</p><p><b>RESULTS</b>There were significant differences in the gene expressions of the PZ cells between the old and young groups. Based on the fold change ratio of > or = 2 or < or = 0.5, 509 up-regulated and 188 down-regulated genes were selected in the PZ cells. A subset of significantly differential genes influencing the growth of adjacent epithelial cells were identified, including HGF, IGF2, IGFBP5 and MMP1 in the old males.</p><p><b>CONCLUSION</b>Stromal cells in the prostate PZ were more active in older males in promoting the malignant progression of adjacent prostate epithelial cells, which might be due to the increased expression of extracellular paracrining mediators.</p>

Primary stromal cells isolated from human various histological/pathological prostate have different phenotypes and tumor promotion role / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prostate stromal cells are known to regulate epithelial growth as well as support and maintain epithelial function. However, how stromal cells regulate epithelial cells and what differences among various histological/pathological prostate stromal cells in prostate cancer progression still remain unclear. This study aimed to investigate the different phenotypes of human various histological/pathological prostate stromal cells, and their role in tumor promotion.</p><p><b>METHODS</b>The different phenotypes of the human normal prostatic peripheral zonal primary stromal cells (NPPF), transitional zonal primary stromal cells (NPTF), and prostate cancer associated primary stromal cells (CAF) were examined with growth curves and Annexin V-fluorescein isothiocyanate (FITC) assay. The different effects on prostate cancer cell line C4-2B by NPPF, NPTF, and CAF were examined with MTT assay and Annexin V-FITC assay. The gene expression of different histological/pathological prostate stromal cells was profiled by microarray and hierarchical cluster analysis.</p><p><b>RESULTS</b>The growth rate of NPPF, NPTF and CAF gradually increased, followed by decreasing apoptosis. In vitro stromal-C4-2B cell line co-culture models, the proliferation and apoptosis of C4-2B cell line were differently affected by human various histological/pathological prostate stromal cells. CAF showed the most powerful effect to C4-2B cell line, as opposed to a weakest effect of NPTF. Microarray and hierarchical cluster analysis showed that the differentially expressed genes of CAF and NPPF were less than NPPF and NPTF, or CAF and NPTF. This was consistent with clinical observations that prostate cancer mostly derived from the peripheral zone and does not usually occur in the transitional zone.</p><p><b>CONCLUSION</b>NPPF, NPTF and CAF possess extremely different biological characteristics and gene expression, which may play an important role in genesis and development of prostate cancer.</p>

Surgical options for benign prostatic hyperplasia: impact on sexual function and risk factors / 中华男科学杂志

Benign prostatic hyperplasia (BPH) is a common problem among elderly males. Surgical resection of the hyperplastic tissue to relieve urinary tract obstruction remains a major option for the treatment of BPH. Operations, whether open prostatectomy, transurethral resection of the prostate, or transurethral laser resection of the prostate, will inevitably affect the sexual function of the patient. With the increased attention to patients' quality of life, more and more importance is being attached to the changes in post-BPH sexual function. This review covers the sexual function changes induced by different surgical methods and assesses the possible risk factors of BPH surgery.

Characterization of stromal cell cultures from the prostatic peripheral zone of men at different ages / 中华男科学杂志

<p><b>OBJECTIVE</b>To characterize age-related cellular phenotype alterations and growth rates of human prostatic stromal cell cultures from the normal prostatic peripheral zone of young donors (PZ-young) and old donors (PZ-old).</p><p><b>METHODS</b>We isolated stromal cells from 10 donors of different ages, assessed the cellular phenotypes by immunocytostaining for prolyl-4-hydroxylase, alpha-smooth muscle actin (alpha-SMA) and desmin, and analysed the ultrastructure by transmission electron microscopy (TEM). The proliferation and apoptosis of the cells were determined by Cell Counting Kit-8 assay and flow cytometry, respectively.</p><p><b>RESULTS</b>All the stromal cells were positive for prolyl-4-hydroxylase regardless of the donors' age, while alpha-SMA and desmin positive cells increased with their age. The positive expressions of alpha-SMA and desmin were (2.56 +/- 1.81)% and (0.89 +/- 0.93)% in PZ-young, and (38.89 +/- 11.22)% and (14.89 +/- 5.97)% in PZ-old (P < 0.01). The alpha-SMA- and/or desmin-positive stromal cells were morphologically large, flat and polygonal. Ultrastructural analysis showed that the cell cultures from PZ-old were richer in rough endoplasmic reticulum and golgi complexes. The stromal cells of PZ-old had a lower growth rate than that of PZ-young (P < 0.01), but there was no significant difference in the apoptosis rate between the two groups.</p><p><b>CONCLUSION</b>Cellular phenotypes of human prostate stromal cell cultures change with the increase of age from predominantly typical fibroblasts to a mixture of fibroblasts and myofibroblasts, which might responsible for the high incidence of prostate cancer in elderly men.</p>

Stem cell-based therapy for erectile dysfunction / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the effect of stem cells in erectile dysfunction as well as their application to the therapy of erectile dysfunction.</p><p><b>DATA SOURCES</b>The data used in the present article were mainly from PubMed with relevant English articles published from 1974 to 2011. The search terms were "stem cells" and "erectile dysfunction".</p><p><b>STUDY SELECTION</b>Articles regarding the role of stem cells in erectile dysfunction and their application to the therapy of erectile dysfunction were selected.</p><p><b>RESULTS</b>Stem cells hold great promise for regenerative medicine because of their ability to self-renew and to differentiate into various cell types. Meanwhile, in preclinical experiments, therapeutic gene-modified stem cells have been approved to offer a novel strategy for cell therapy and gene therapy of erectile dysfunction.</p><p><b>CONCLUSION</b>The transplantation of stem cells has the potential to provide cell types capable of restoring normal function after injury or degradation in erectile dysfunction. However, a series of problems, such as the safety of stem cells transplantation, their application in cell therapy and gene therapy of erectile dysfunction need further investigation.</p>

Proportion of intermediate epithelial cells and human prostate cancer / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the different proportions of intermediate epithelial cells in human prostate cancer tissue and their clinical significance.</p><p><b>METHODS</b>We performed immunohistochemical staining for Cytokeratin 5 (CK5) and Cytokeratin 8 (CK8) on 60 samples of human prostate cancer, determined the proportions of intermediate epithelial cells in the cancer tissue, and classified the samples into 2 types, one with a majority of intermediate epithelial cells (CaP-INT, n = 32), and the other composed mostly of luminal epithelial cells (CaP-LUM, n = 28). Then we compared the 2 types of prostate cancer in the expression of the androgen receptor (AR), age of the patient, serum t-PSA, prostate volume, Gleason score, clinical stage, androgen resistance, and incidence of distant metastasis.</p><p><b>RESULTS</b>CaP-INT showed a significantly lower expression of AR ([24.42 +/- 11.41] %) and a higher incidence of distant metastasis (n = 14) than CaP-LUM ([77.21 +/- 10.22] % and n = 4) (P < 0.05). In the CaP-INT group, 6 of the 26 endocrinologically treated cases developed into androgen-independent prostate cancer (AIPC), while in the CaP-LUM group, only 1 out of 23 (P < 0.05). The former also showed remarkably higher clinical stages than the latter (P < 0.05), but no significant differences were found in age, serum t-PSA, prostate volume and Gleason score between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>A higher proportion of intermediate epithelial cells may lead to increased invasiveness and metastasis of human prostate cancer.</p>

Targeted degradation of androgen receptors in androgen-independent prostate cancer cells: an experimental study / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate targeted degradation of the androgen receptor (AR) by chimeric molecules (DHT-PROTAC) via the ubiquitin-proteasome pathway in androgen-independent prostate cancer CA-2B cells, and explore the proliferation, secretion and apoptosis of the treated cells.</p><p><b>METHODS</b>C4-2B cells were treated with DHT-PROTAC, and then the expressions of the AR protein and caspase3 in the C4-2B cells were detected by immunohistochemistry and Western blot. The concentration of PSA in the supernatant was examined by ELISA. The cells were counted and their proliferation analyzed by a growth curve. The inhibitory effect on the growth of C4-2B cells was evaluated by MIT assay.</p><p><b>RESULTS</b>Compared with the control group, the DHT-PROTAC-treated group showed an obviously decreased expression of AR proteins with a significant attenuation of the band signals (P < 0.05), a 40% reduction of the AR-positive cells and a 60% decrease of the PSA concentration in the supernatant (P < 0.05). DHT-PROTAC exhibited an inhibitory effect on the C4-2B cells in a time-dependant manner (P < 0.05).</p><p><b>CONCLUSION</b>The chimeric molecule (DHT-PROTAC) can target the degradation of androgen receptors, reduce the secretion of PSA and repress the in vitro growth of C4-2B cells.</p>

An update of biomarkers in prostate cancer tissue / 中华男科学杂志

The development of biomarkers for prostate cancer screening, detection and prognosis has greatly decreased the mortality of this disease. Recently, some new views on such biomarkers as PSMA, CK34betaE12, p63, AMACR, Pca-24, hTERT, DD3, Annexin A3 and GSTP1 methylation in prostate cancer tissue have been re-identified and investigated. Future research should focus on the combined screening of multiple biomarkers and discovery of new ones, which may possibly improve the sensitivity, specificity and accuracy of the early detection of prostate cancer.

Small incision combined with laparoscopy for ureteropelvic junction obstruction: comparison with retroperitoneal laparoscopic pyeloplasty / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Laparoscopic dismembered pyeloplasty is technically feasible for ureteropelvic junction (UPJ) obstruction although it is still challenged by its technical difficulty and time-consuming. In this study, we compared the initial results of retroperitoneal laparoscopic pyeloplasty versus a combined laparoscopic dissection and open reconstruction through a small incision in the treatment of UPJ obstruction.</p><p><b>METHODS</b>Sixty-four patients with primary UPJ obstruction underwent pyeloplasty: 32 patients underwent laparoscopic procedure and 32 patients underwent open assisted laparoscopic surgery including two steps, ie, laparoscopic dissection of the UPJ transperitoneally and then pyeloplasty via an extended small incision. The demographic data and intraoperative, postoperative and follow-up conditions of patients were compared between the two groups.</p><p><b>RESULTS</b>Preoperative data were comparable in the patients of the two groups. The operative time was shorter (60.9 minutes vs 157.7 minutes, P < 0.0001) and the complication rate was lower (9.4% vs 31.3%, P < 0.05) in the open assisted group than in the laparoscopic group. The estimated blood loss (42.3 ml vs 47.8 ml), time to have normal diet (37.6 hours vs 33.8 hours), and hospital stay (6.7 days vs 6.2 days) were equivalent. The operative success rate was 97% for the open assisted group and 91% for the laparoscopic group.</p><p><b>CONCLUSIONS</b>The procedure of combined small incision with laparoscopy for UPJ obstruction is technically easy, and the results are promising. It can be used as an alternative to conventional procedures.</p>

Androgen receptor functioned as a suppressor in the prostate cancer cell line PC3 in vitro and in vivo / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prostate cancer is one of the most common urogenital tumors in the world with an increasing incidence in China. Androgen deprivation therapy is the major therapeutic option for advanced prostate cancer. However, the role of androgen receptor (AR) in hormone-refractory prostate cancer still remains unclear. This work aimed to investigate the role of AR in an androgen independent prostate cancer cell line by in vitro and in vivo studies.</p><p><b>METHODS</b>The role of AR in the proliferation and invasion/metastasis ability of PC3-AR9 (a PC3 stable clone expressing human AR driven by natural human AR promoter) were examined with MTT assay, soft agar assay, chamber invasion assay, wound healing assay, and also with orthotopic xenograft mouse model.</p><p><b>RESULTS</b>Restoring androgen receptor in PC3 cells resulted in decreased proliferation and invasion/metastasis ability in MTT, soft agar, chamber invasion and wound healing assay. In the mouse orthotopic xenograft model, PC3-AR9 resulted in smaller primary tumors and metastasis tumors, with a lower proliferation rate and higher apoptosis rate.</p><p><b>CONCLUSION</b>The AR might function as a tumor suppressor in PC3 cells both in vitro and in vivo.</p>

Chimeric molecules facilitate the degradation of androgen receptors and repress the growth of LNCaP cells / 亚洲男科学杂志(英文版)

Post-translational degradation of protein plays an important role in cell life. We employed chimeric molecules (dihydrotestosterone-based proteolysis-targeting chimeric molecule [DHT-PROTAC]) to facilitate androgen receptor (AR) degradation via the ubiquitin-proteasome pathway (UPP) and to investigate the role of AR in cell proliferation and viability in androgen-sensitive prostate cancer cells. Western blot analysis and immunohistochemistry were applied to analyse AR levels in LNCaP cells after DHT-PROTAC treatment. Cell counting and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay were used to evaluate cell proliferation and viability after AR elimination in both LNCaP and PC-3 cells. AR was tagged for elimination via the UPP by DHT-PROTAC, and this could be blocked by proteasome inhibitors. Degradation of AR depended on DHT-PROTAC concentration, and either DHT or an ALAPYIP-(arg)(8) peptide could compete with DHT-PROTAC. Inhibition of cell proliferation and decreased viability were observed in LNCaP cells, but not in PC-3 or 786-O cells after DHT-PROTAC treatment. These data indicate that AR elimination is facilitated via the UPP by DHT-PROTAC, and that the growth of LNCaP cells is repressed after AR degradation.