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1.
Mol Med Rep ; 18(5): 4733-4738, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30221721

ABSTRACT

The aim of the present study was to investigate the acute effect and mechanism of tumor necrosis factor (TNF) on basolateral 50 pS K channels in the thick ascending limb (TAL) of the rat kidney. The TAL tubules were isolated from the rat kidney, and the activity of the 50 pS K channels was recorded using the patch­clamp technique. The results indicated that the application of TNF (10 nM) significantly activated the 50 pS K channels and the TNF effect was concentration­dependent. Inhibition of protein kinase A, phospholipase A2 and protein tyrosine kinase using pathway inhibitors (H89, AACOCF3 and Herbimycin A, respectively) did not abolish the stimulatory effect of TNF, indicating that none of these pathways mediated the TNF effect. By contrast, the phenylarsine oxide inhibitor against protein tyrosine phosphatase (PTP) decreased the activity of the 50 pS K channels and blocked the stimulatory effect of TNF on these channels. Furthermore, western blot analysis demonstrated that the application of TNF (10 nM) in the TAL increased the phosphorylation of PTP, an indication of PTP activity stimulation. Thus, it was concluded that the acute application of TNF may stimulate the basolateral 50 pS K channel in the TAL and the stimulatory effect of TNF may be mediated by the PTP­dependent pathway.


Subject(s)
Kidney Tubules/metabolism , Kidney/metabolism , Potassium Channels/genetics , Tumor Necrosis Factor-alpha/metabolism , Animals , Arachidonic Acids/administration & dosage , Arsenicals/administration & dosage , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/metabolism , Isoquinolines/administration & dosage , Kidney/drug effects , Kidney/pathology , Kidney Tubules/drug effects , Loop of Henle/drug effects , Loop of Henle/metabolism , Male , Patch-Clamp Techniques , Phospholipase A2 Inhibitors/administration & dosage , Phospholipases A2/genetics , Potassium Channels/metabolism , Protein Tyrosine Phosphatases/antagonists & inhibitors , Protein Tyrosine Phosphatases/metabolism , Protein-Tyrosine Kinases/antagonists & inhibitors , Rats , Rats, Sprague-Dawley , Rifabutin/administration & dosage , Rifabutin/analogs & derivatives , Sulfonamides/administration & dosage , Tumor Necrosis Factor-alpha/administration & dosage
2.
Int J Oncol ; 53(1): 358-370, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29749439

ABSTRACT

The present study aimed to examine the effects and mechanisms of exogenous C-X-C motif chemokine 5 (CXCL5) and lentiviral CXCL5 overexpression on the regulation of malignant behaviors of prostate cancer cells in vitro and in a nude mouse xenograft model. The expression levels of CXCL5 and a number of tumor-related genes were assessed by using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, ELISA, or immunohistochemistry in normal and cancerous prostate cells and tissues. Cell proliferation, colony formation, and Transwell assays were performed to determine the effects of exogenous, autocrine, and paracrine CXCL5 on prostate cancer cell proliferative and migratory capacity. The results indicated that CXCL5 expression was upregulated in PC­3 and DU145 prostate cancer cells, in WPMY­1 normal prostate stromal cells, and in RWPE­1 prostate epithelial cells, as well as in prostate cancer tissue specimens. Exogenous CXCL5 exposure resulted in increase in prostate cancer cell proliferation, colony formation, and migration. In cells transfected with a CXCL5 overexpression vector, in cells cultured in conditioned medium from CXCL5-overexpressing WPMY cells, and in cells co-cultured with CXCL5­OE WPMY cells prostate cancer cell malignant phenotypes were induced in an autocrine/paracrine fashion in vitro; similar results were observed in nude mouse xenografts. CXCL5 overexpression also regulated expression of tumor-related genes, including BAX, N-Myc downstream-regulated gene 3, extracellular signal-regulated kinase 1/2, C-X-C chemokine receptor type 2, interleukin 18, Bcl­2, and caspase­3. These data demonstrated that CXCL5 expression was upregulated in prostate cancer tissues and that exogenous CXCL5 protein exposure or CXCL5 overexpression promoted malignant phenotypes of prostate cancer cells in vitro and in vivo.


Subject(s)
Cell Proliferation/genetics , Chemokine CXCL5/genetics , Neoplasm Proteins/genetics , Prostatic Neoplasms/genetics , Animals , Autocrine Communication/genetics , Cell Line, Tumor , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Humans , Lentivirus/genetics , Male , Mice , Paracrine Communication/genetics , Prostatic Neoplasms/pathology , Signal Transduction/genetics , Stem Cells , Xenograft Model Antitumor Assays
3.
Exp Ther Med ; 15(1): 847-853, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29399089

ABSTRACT

For several thousand years, Ganoderma lucidum (Ling-Zhi in Chinese and Reishi in Japanese) has been widely used as a traditional medication for the prevention and treatment of various diseases in Asia. Its major biologically active components, ganoderic acids (GAs), exhibit significant medicinal value due to their anti-inflammatory effects. Dysregulation of microglial function may cause seizures or promote epileptogenesis through release of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. At present, only little information is available on the effects of GAs on microglia-mediated inflammation in vitro and/or in vivo. The present study aimed to investigate the role of GA-A on microglia-mediated inflammation in vitro. In addition, the effect of GA-A on lipopolysaccharide (LPS)-evoked alterations in mitochondrial metabolic activity of microglia was evaluated. The results of the present study demonstrated that GA-A significantly decreased LPS-induced IL-1ß, IL-6 and TNF-α release from mouse-derived primary cortical microglial cells in a concentration-dependent manner. GA-A treatment reduced LPS-induced expression of nuclear factor (NF)-κB (p65) and its inhibitor, demonstrating that non-toxic suppression of IL-1ß, IL-6 and TNF-α production by GA-A is, at least in part, due to suppression of the NF-κB signaling pathway. In addition, the LPS-induced stimulation of mitochondrial activity of microglial cells was abolished by co-treatment with GA-A. Thus, GA-A treatment may be a potential therapeutic strategy for epilepsy prevention by suppressing microglia-derived proinflammatory mediators.

4.
Zhonghua Nan Ke Xue ; 23(1): 27-33, 2017 Jan.
Article in Chinese | MEDLINE | ID: mdl-29658233

ABSTRACT

OBJECTIVE: To investigate the anti-prostate cancer (PCa) effect of roemerine in vitro and in vivo in the mouse model of PCa. METHODS: We detected the effects of roemerine on the proliferation, apoptosis and migration of PCa cells DU145, LNCaP, PC-3 and 22RV1, screened out the sensitive cell line and constructed a tumor-bearing model in mice for verification of the antitumor efficacy of roemerine in vivo. RESULTS: Roemerine inhibited the proliferation and migration of the DU145, LNCaP, PC-3 and 22RV1 cells and induced their apoptosis in different degrees, particularly those of the LNCaP cells. The average tumor weight was less in the roemerine intervention group (ï¼»1.99±0.95ï¼½ g) than in the control (ï¼»2.95±1.04ï¼½ g), the least in the high-dose roemerine (30 mg/kg) plus paclitaxel intervention group (ï¼»0.90±0.16ï¼½ g). The mean heart, liver, and kidney indexes were markedly lower in the roemerine (0.58±0.06, 6.20±0.42 and 1.49±0.33) than in the paclitaxel group (0.66±0.04, 6.99±0.72 and 1.95±0.34), while the mean spleen and thymus indexes were remarkably higher in the former (0.54±0.11 and 0.06±0.01) than in the latter (0.41±0.09 and 0.05±0.01). Pathological staining showed a lower degree of malignancy and metastasis in both the roemerine and the roemerine + paclitaxel intervention group than in the control, as well as a lower degree of visceral injury in the roemerine and roemerine + paclitaxel groups than in the paclitaxel group. CONCLUSIONS: Roemerine has some anti-PCa effect and alleviates adverse reactions in paclitaxel combination administration.


Subject(s)
Alkaloids/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Prostatic Neoplasms/drug therapy , Animals , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Disease Models, Animal , Drug Therapy, Combination/methods , Male , Mice , Mice, Nude , Paclitaxel/adverse effects , Paclitaxel/therapeutic use
5.
Int Urol Nephrol ; 48(5): 701-9, 2016 May.
Article in English | MEDLINE | ID: mdl-26837773

ABSTRACT

PURPOSE: CXCL3 and its receptor CXCR2 were considered to play particularly important roles in the progression of malignancies. However, the investigations about CXCL3/CXCR2 axis in prostate cancer have been poorly involved. Herein we firstly reported our studies on the expression and biological roles of CXCL3 and CXCR2 in prostate cancer. METHODS: Expression levels of CXCL3 and CXCR2 in prostate cancer cell lines (PC-3, DU145 and LNCaP), immortalized prostate stromal cell line (WPMY-1) and immortalized prostate epithelial cell line (RWPE-1) were investigated by RT-PCR, ELISA and western blot, whereas expression levels of CXCL3 in a prostate tissue microarray were detected by immunohistochemistry. Cell counting kit-8 and transwell assays were, respectively, utilized to determine the effects of exogenous CXCL3 on the cell proliferation and migration. We further examined whether CXCL3 could regulate the expression of genes correlated with prostate tumorigenesis by RT- PCR. RESULTS: Elevated expression of CXCR2 was detected in DU145, LNCaP and RWPE-1. Moreover, high-level CXCL3 can be secreted by PC-3 and RWPE-1, and CXCL3 protein expression level in tissue microarray is concordant with prostate cancer metastasis. Exogenous CXCL3 does not contribute to proliferation, but has a significant effect on migration of prostate cancer cells and RWPE-1. Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3. CONCLUSION: Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis.


Subject(s)
Chemokines, CXC/genetics , Gene Expression Regulation, Neoplastic/drug effects , Prostatic Neoplasms/genetics , RNA, Messenger/metabolism , Receptors, Interleukin-8B/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Chemokines, CXC/metabolism , Chemokines, CXC/pharmacology , Epithelial Cells/metabolism , Humans , Intracellular Signaling Peptides and Proteins , Male , Membrane Proteins/genetics , Nerve Tissue Proteins/genetics , Prostate/cytology , Prostate/metabolism , Prostatic Neoplasms/metabolism , Receptors, Interleukin-8B/metabolism , Stromal Cells/metabolism , Tumor Protein p73/genetics , bcl-2-Associated X Protein/genetics
6.
Oncol Lett ; 10(2): 647-652, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26622548

ABSTRACT

DNA methylation is one of the major mechanisms via which tumor suppressor gene inactivation occurs. For example, hypermethylation of the promoter region of cadherin 11 (CDH11), a novel tumor suppressor gene, frequently occurs in human cancer. In the current study, the methylation status of CDH11 was investigated in bladder cancer tissue samples, and the correlation with clinicopathological features and patient outcome was assessed. The methylation status of CDH11 was detected in 146 bladder cancer tissues and 37 normal bladder epithelial tissues using methylation-specific polymerase chain reaction (PCR). In addition, CDH11 mRNA expression levels were examined by quantitative PCR. Subsequently, associations between CDH11 methylation and specific clinicopathological characteristics, as well as patient outcome, were analyzed. Aberrant CDH11 promoter hypermethylation was detected in 63.0% (92/146) of bladder cancer tissues, however, no CDH11 methylation was identified in the control samples; this difference was significant (P<0.05). Furthermore, CDH11 mRNA expression levels were significantly lower in the tumor samples with methylated CDH11 compared with the normal bladder epithelium and tumor samples with unmethylated CDH11 (P<0.05). When the methylation status of CDH11 was correlated with the clinicopathological features, it was identified that CDH11 methylation was significantly associated with poor differentiation (P=0.0440), an advanced disease stage (P=0.0350), a larger tumor size (P=0.0013) and multiple tumors (P=0.0390). In addition, patients with methylated CDH11 exhibited significantly poorer outcomes than patients with unmethylated CDH11 (P=0.0004). Furthermore, multivariate Cox proportional hazard analysis indicated that CDH11 methylation was independently associated with a poor outcome in the patients with bladder cancer, with a relative risk of mortality of 6.852 (P=0.0082; 95% confidence interval, 3.461-16.177). The current findings indicate that aberrant CDH11 methylation frequently occurs in bladder cancer, and correlates with malignant behavior and poor outcome. Thus, CDH11 methylation status may be used as an independent prognostic biomarker for patients with bladder cancer.

7.
Med Sci Monit ; 21: 2870-6, 2015 Sep 25.
Article in English | MEDLINE | ID: mdl-26404644

ABSTRACT

BACKGROUND: Protocadherin17 (PCDH17) is a tumor suppressor gene, and is frequently silenced by promoter methylation in human cancers, including clear cell renal cell carcinoma (ccRCC). However, the clinical significance of PCDH17 methylation in ccRCC remains largely unclear. The aim of the present study was to investigate the methylation status of PCDH17 in ccRCC and its potential relevance to clinicopathological parameters and prognosis. MATERIAL AND METHODS: Methylation-specific PCR was used to examine the methylation status of PCDH17 in 191 ccRCC tumors and matched paired adjacent noncancerous tissues. Subsequently, the associations between PCDH17 methylation and clinicopathological parameters and prognosis of patients with ccRCC were analyzed. RESULTS: PCDH17 methylation occurred in 66.5% of ccRCC tumors, but in only 12.1% of adjacent noncancerous tissues. PCDH17 methylation is significantly correlated with advanced stage, higher grade, and lymph node metastasis in ccRCC. Moreover, it is an independent prognostic factor for progression-free survival and overall survival of patients with ccRCC. CONCLUSIONS: PCDH17 methylation occurred more frequently and was associated with malignant clinicopathological characteristics and poor prognosis in ccRCC patients. Thus, PCDH17 methylation may be used as a novel biomarker to predict the prognosis of patients with ccRCC.


Subject(s)
Cadherins/genetics , Carcinoma, Renal Cell/genetics , DNA Methylation , Kidney Neoplasms/genetics , Promoter Regions, Genetic , Aged , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/metabolism , CpG Islands , Disease-Free Survival , Female , Humans , Kidney/metabolism , Kidney/pathology , Kidney Neoplasms/metabolism , Lymphatic Metastasis , Male , Middle Aged , Polymerase Chain Reaction , Prognosis , Real-Time Polymerase Chain Reaction
8.
Med Sci Monit ; 20: 2584-9, 2014 Dec 08.
Article in English | MEDLINE | ID: mdl-25486497

ABSTRACT

BACKGROUND: Protocadherin8 has been demonstrated to play critical roles in initiation and progression of several human cancers. It is frequently inactivated by promoter methylation in cancers and may be used as a potential biomarker. However, the methylation status of protocadherin8 and its clinical significance in prostate cancer remains largely unknown. The purpose of this study was to evaluate the clinical significance of protocadherin8 methylation in early-stage prostate cancer. MATERIAL AND METHODS: The promoter methylation status of protocadherin8 in 162 prostate cancer tissues and 47 normal prostate tissues was examined using methylation-specific PCR (MSP). Subsequently, the relationships between protocadherin8 methylation and clinicopathological features of prostate cancer patients and biochemical recurrence-free survival of patients were analyzed. RESULTS: We found that protocadherin8 methylation occurred frequently in prostate cancer tissues but not in normal prostate tissues. Moreover, protocadherin8 methylation was significantly associated with advanced pathologic stage, higher level of preoperative prostate specific antigen (PSA), higher Gleason score, positive lymph node metastasis, and biochemical recurrence. In addition, patients with protocadherin8 methylated have shorter biochemical recurrence-free survival time than patients without. Multivariate Cox regression analysis revealed that protocadherin8 methylation was an independent predictor of biochemical recurrence-free survival in prostate cancer patients. CONCLUSIONS: Promoter methylation of protocadherin8 is a frequent event in prostate cancer, and might be used as an independent prognostic factor for biochemical recurrence-free survival in patients with prostate cancer.


Subject(s)
Cadherins/genetics , DNA Methylation/genetics , Neoplasm Recurrence, Local/genetics , Promoter Regions, Genetic , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Aged , Disease-Free Survival , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Polymerase Chain Reaction , Prognosis , Proportional Hazards Models , Protocadherins
9.
J Int Med Res ; 42(1): 35-41, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24366498

ABSTRACT

OBJECTIVE: To investigate the prognostic value of protocadherin 17 (PCDH17) promoter methylation in serum-derived DNA of patients with bladder cancer. METHODS: DNA was isolated from serum of patients with bladder cancer and from age- and sex-matched controls. Methylation-specific polymerase chain reaction was used to examine the methylation status of the PCDH17 promoter. The correlations between methylation status and clinicopathological characteristics and overall survival were examined. RESULTS: PCDH17 promoter methylation was detected in 79/151 (52.3%) of patients with bladder cancer, and none of the 43 control subjects. Methylation was significantly associated with larger tumour diameter (>3 cm), high grade (G3) and advanced stage (T2-T4). Patients with PCDH17 promoter methylation had significantly shorter overall survival than those with unmethylated PCDH17 promoter. Methylation was an independent predictor of overall survival. CONCLUSIONS: PCDH17 promoter methylation was significantly associated with malignant behaviour and poor prognosis of bladder cancer. The detection of PCDH17 promoter methylation in serum-derived DNA may be a convenient and noninvasive predictive biomarker in routine clinical practice.


Subject(s)
Biomarkers, Tumor/genetics , Cadherins/genetics , DNA Methylation , DNA/blood , Promoter Regions, Genetic , Urinary Bladder Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , DNA Primers , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Prognosis , Urinary Bladder Neoplasms/blood , Urinary Bladder Neoplasms/pathology , Young Adult
10.
Zhonghua Nan Ke Xue ; 18(2): 126-9, 2012 Feb.
Article in Chinese | MEDLINE | ID: mdl-22568208

ABSTRACT

OBJECTIVE: To study the correlation of homocysteine (Hcy) in plasma with nitric oxide synthetase (NOS) and endogenous carbon monoxide (CO) in the penile corpus cavernosum of type 2 diabetic rats. METHODS: This study included 40 male Wistar rats, 10 as controls (Group A) and the other 30 as diabetes mellitus (DM) models. Four weeks after the model establishment, the model rats were divided into a DM group (Group B, n = 10), an insulin treated group (Group C, n = 10), and a folic acid and vitamin B12 treated group (Group D, n = 10). All the rats were injected with apomorphine and observed for penile erection at 8 and 12 weeks, and the levels of total plasma Hcy (tHcy), NOS and CO in the penile corpus cavernosum were measured at 12 weeks. RESULTS: Compared with Group A, the level of tHcy was significantly increased, while NOS and CO activities in the penile cavernous tis-sue and erectile function remarkably decreased in Group B (P < 0.01). The incidence rate of high Hcy was 55% in the DM rats. In comparison, the level of tHcy was obviously decreased, and the NOS activity and erectile function markedly increased in Groups C and D (P < 0.01). The Hcy level showed a significant negative correlation with NOS activity (rA = -0.89, rB = -0.76, rc = -0.91, rD = -0.91) and CO content (TA = -0.82, r, = -0.77, rc = -0.93, rD = -0.81). CONCLUSION: High plasma Hcy can decrease NOS and CO activities in the penile corpus cavernosum, and consequently induce erectile dysfunction in DM rats, while insulin, folic acid and vitamin B12 can improve their penile erectile function by increasing NOS and CO activities.


Subject(s)
Carbon Monoxide/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Type 2/blood , Homocysteine/blood , Nitric Oxide Synthase/metabolism , Penis/metabolism , Animals , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Folic Acid/pharmacology , Insulin/pharmacology , Male , Penis/drug effects , Rats , Rats, Wistar , Vitamin B 12/pharmacology
11.
Zhonghua Nan Ke Xue ; 15(6): 523-5, 2009 Jun.
Article in Chinese | MEDLINE | ID: mdl-19593992

ABSTRACT

OBJECTIVE: To investigate the effects of CO release inhibitor zinc protoporphyria IX (ZnPP IX) and NO release inhibitor L-NAME on the content of cGMP in the penile tissue of rats. METHODS: Thirty Wistar rats were randomly divided into a normal control, a ZnPP IX, and an L-NAME group, given saline (1 ml/kg/d), ZnPP IX (45 micromol/kg/d) and L-NAME (50 mg/kg/d), respectively, for 7 days. Then all the rats were killed, homogenate made from their penile tissues and detected for the contents of NOS, NO, CO and cGMP. RESULTS: The contents of CO, NOS, NO and cGMP were all reduced in both the ZnPP IX and L-NAME groups as compared with the control group (P < 0.05). CONCLUSION: ZnPP IX and L-NAME can reduce the concentrations of CO and NO in the penile tissues of rats, and consequently the content of cGMP.


Subject(s)
Carbon Monoxide/metabolism , Cyclic GMP/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , Penis/metabolism , Protoporphyrins/pharmacology , Animals , Carbon Monoxide/antagonists & inhibitors , Male , Nitric Oxide/antagonists & inhibitors , Penis/drug effects , Rats , Rats, Wistar
12.
Zhonghua Nan Ke Xue ; 15(2): 122-5, 2009 Feb.
Article in Chinese | MEDLINE | ID: mdl-19323370

ABSTRACT

OBJECTIVE: To explore the relationship of aging with the changes of endogenous carbon monoxide (CO), cGMP and cAMP contents in the penile tissues of rats. METHODS: Twenty-four male rats were equally divided into an 8-month, a 16-month and a 24-month group, and their penile erection was detected by injecting apomorphine, their penile cavernous body harvested, and the contents of CO, cAPM and cGMP detected by improved dual wavelength spectrophotometry. RESULTS: The contents of CO, cAPM and cGMP were reduced with the increase of age, with statistically significant differences between the three age groups (P < 0.01). CONCLUSION: Aging significantly decreased the contents of CO, cAMP and cGMP in the penile tissues of the rats, which suggests that aging might play an important role in erectile dysfunction.


Subject(s)
Aging/physiology , Carbon Monoxide/metabolism , Cyclic AMP/metabolism , Cyclic GMP/metabolism , Penis/metabolism , Animals , Male , Rats , Rats, Wistar
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