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AIM: To explore the correlation between Fat mass and objectivity associated gene (FTO) rs9939609 polymorphism and susceptibility to polycystic ovary syndrome. METHODS: Case-control studies on the relationship between FTO rs9939609 A/T polymorphism and PCOS were searched in PubMed, EMBASE, and Web of Science according to inclusion and exclusion criteria. STATA 12.0 software was conducted for Meta-analysis. RESULTS: Nine case-control studies were included, including 1410 cases in PCOS group and 1223 cases in healthy control group. The results of meta-analysis showed that FTO rs9939609 gene polymorphism was associated with PCOS susceptibility, and the risk of developing PCOS was 1.19 times higher for T alleles carriers than for A alleles carriers, and some similar associations were observed in Asian populations. CONCLUSIONS: In summary, FTO rs9939609 gene polymorphism is significantly associated with PCOS susceptibility, especially in Asian populations.
ABSTRACT
Inflammation and immune responses play important roles in cancer development and prognosis. We identified 59 upregulated inflammation- and immune-related genes (IIRGs) in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas database. Among the upregulated IIRGs, nucleotide binding oligomerization domain 2 (NOD2), PYD and CARD domain (PYCARD) were also confirmed to be upregulated in the Oncomine database and in three independent GEO data sets. Tumor immune infiltration resource database analysis revealed that NOD2 and PYCARD levels were significantly positively correlated with infiltration levels of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages and dendritic cells. Multivariate Cox hazards regression analysis indicated that based on clinical variables (age, gender, tumor grade, pathological TNM stage), NOD2, but not PYCARD, was an independent, unfavorable ccRCC prognostic biomarker. Functional enrichment analyses (GSEA) showed that NOD2 was involved in innate immune responses, inflammatory responses, and regulation of cytokine secretion. Meanwhile, mRNA and protein levels of NOD2 were elevated in four ccRCC cell lines (786-O, ACHN, A498 and Caki-1), and its knockdown significantly inhibited IL-8 secretion, thereby inhibiting ccRCC cell proliferation and invasion. Furthermore, results showed that miR-20b-5p targeted NOD2 to alleviate NOD2-mediated IL-8 secretion. In conclusion, NOD2 is a potential prognostic biomarker for ccRCC and the miR-20b-5p/NOD2/IL-8 axis may regulate inflammation- and immune-mediated tumorigenesis in ccRCC.
Subject(s)
Carcinoma, Renal Cell , Carcinoma , Kidney Neoplasms , MicroRNAs , Humans , Carcinoma, Renal Cell/genetics , Prognosis , Interleukin-8/genetics , Inflammation/genetics , Kidney Neoplasms/genetics , Biomarkers , MicroRNAs/genetics , Nod2 Signaling Adaptor Protein/geneticsABSTRACT
The aim of this study was to analyze the pollution degree and causes of soil and agricultural products in high geological background areas and to provide a basis for the safe production of agricultural products and the risk control of soil heavy metals. A total of 36 sets of soil-corn collaborative samples were collected in the farming area of Baolong Town, Wushan County, Chongqing City; the contents of heavy metals (Cd, Hg, Pb, As, and Cr) and soil pH in the soil-maize were analyzed, the pollution degree of heavy metals in the soil-maize was evaluated using the Nemerow comprehensive pollution index method (PN) and comprehensive quality impact index (IICQ). The sources of heavy metals in the soil and the influencing factors of heavy metal excess in corn were also analyzed. The results showed that the average value of soil heavy metal content in the study area was higher than the national and Chongqing soil background values, and the soil heavy metal enrichment effect was obvious. Cd was the main factor of soil-maize exceeding the standard, and the overall exceeding rates of soil and corn Cd were 91.67% and 30.55%, respectively. The evaluation results of the Nemerow comprehensive pollution index showed that the soil was dominated by heavy pollution, accounting for 63.89%. The soil-maize comprehensive quality impact index was dominated by moderate and severe pollution, accounting for 44.44% and 47.22%, respectively. From the perspective of the spatial distribution of heavy metal pollution, corn and soil pollution areas were inconsistent. Soil heavy metal pollution was mainly affected by the Permian and Triassic strata and was related to the secondary enrichment of black rock series and limestone areas. The Cd content of maize was mainly affected by soil pH, and maize was relatively safe under alkaline conditions. It is suggested that the soil in the study area should be divided into risk zones according to the stratum distribution, and the planting structure should be adjusted in the high-risk areas. For the low- and medium-risk areas, it is recommended to strengthen the monitoring of agricultural inputs and reduce the input of heavy metals in the soil. Additionally, we recommend carrying out agronomic regulation in acidic soil areas to improve soil acidification, plant corn varieties with low accumulation of heavy metals, and reduce the risk of agricultural products exceeding the standard.
ABSTRACT
In order to identify the source of heavy metals in the soil around a mining area and provide effective suggestions for the prevention and control of regional soil pollution, 118 topsoil samples (0-20 cm) were collected in the northern part of Wuli Township, Qianjiang District, Chongqing. The heavy metal (Cd, Hg, Pb, As, Cr, Cu, Zn, and Ni) contents in the soil and soil pH were analyzed, and the spatial distribution and sources of heavy metals in the soil were studied using the geostatistical method and APCS-MLR receptor model. The results showed that the content of heavy metals in the soil was significantly higher than the background value in Chongqing; there was obvious surface accumulation; and Hg, Pb, Cd, As, and Zn showed strong variation. The proportions of soil Cd, Hg, Pb, As, and Zn exceeding the risk screening values were 47.11%, 6.61%, 4.96%, 5.79%, and 7.44%, respectively, and the proportions of soil Cd, Hg, Pb, and As exceeding the risk control values were 0.83%, 4.13%, 0.83%, and 0.83%; thus, the problem of excessive heavy metals in the soil was significant. Soil Cd, As, Cr, Cu, and Ni were mainly affected by soil parent materials, and their contribution rates to the total soil elements were 77.65%, 68.55%, 71.98%, 90.83%, and 82.19%, respectively. Soil Hg, Pb, and Zn were mainly affected by the mining of mercury mines and lead-zinc mines, with the contribution rates of 86.59%, 88.06%, and 91.34%, respectively. In addition, agricultural activities also affected soil Cd and As contents. It is recommended to strengthen the safety monitoring of agricultural products and agricultural inputs, plant varieties with a low accumulation of heavy metals, reduce the use of livestock manure, and grow non-edible agricultural products in areas that exceed the control value of heavy metal pollution risk.
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Background: D-dimer is a fibrin-degrading substance that is soluble and whose degradation is produced by plasma protein-mediated degradation of cross-linked fibrin. Previous investigations have shown a link between D-dimer and the mortality in lung cancer patients. However, different investigations varied whether D-dimer could predict prognosis in these patients. Methods: A meta-analysis and systematic review of all available cohort studies were performed on the link between circulating D-dimer levels and survival of lung cancer patients. Relevant studies were searched in Embase, Cochrane Library, and PubMed databases. Data from 540 lung cancer patients from the First Hospital of Soochow University and Sichuan Cancer Hospital were used for external validation. Results: We finally obtained 19 eligible cohort studies with pooled HR showing that high D-dimer levels contribute to death in tumor group (HR 1.62, 95% CI: 1.39-1.88, I2 = 75.0%). Further stratified analysis showed that higher circulating D-dimer in the advanced lung cancer group was linked to a 1.91-fold risk (HR = 2.91, 95% CI: 2.24-3.78, I2 = 6.0%). Incorporation of other variables, including days of follow-up, country, design, public year, population, disease status, and quality score, into the meta-regression model, indicated that disease status was an additional source of heterogeneity (p < 0.001). External validation of 540 patients also showed that high levels of D-dimer showed a higher risk of overall mortality (HR 1.39, 95% CI: 1.13-1.72, p = 0.002) and VTE events (HR 3.98, 95% CI: 1.99-8.70, p = 0.002) in lung cancer patients. Conclusions: High circulating plasma D-dimer levels independently predict long-term prognosis and the risk of venous thromboembolism in lung cancer.
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The long non-coding RNA (lncRNA) SNHG1 has been shown to be implicated in the progression of multiple human carcinomas. Nevertheless, the biological functions and potential mechanism of SNHG1 in bladder cancer (BC) are uncharacterized. In the present study, SNHG1 was found to be substantially up-regulated in BC tissues and cells and was intimately correlated with the TNM stage, lymphatic invasion, metastasis and recurrence-free survival in BC patients. Down-regulation of SNHG1 dramatically attenuated the proliferation, migration and invasion of BC cells, whereas the ectopic overexpression of SNHG1 had the opposite effects in vitro. The in vivo experimental results also indicated that SNHG1 down-regulation hampered the tumour growth and metastasis of BC cells. Mechanistic investigations revealed that SNHG1 enhances HK2 expression by serving as an endogenous sponge to regulate miR-143-3p in the cytoplasm of BC cells. In the nucleus, SNHG1 could interact with EZH2 and regulate the histone methylation of the CDH1 promoter, altering the biological behaviours of BC cells. Overall, these findings elucidate an oncologic role of SNHG1 in BC and provide a new therapeutic strategy against BC.
Subject(s)
Disease Progression , Enhancer of Zeste Homolog 2 Protein/metabolism , Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Urinary Bladder Neoplasms/genetics , Animals , Antigens, CD/genetics , Base Sequence , Cadherins/genetics , Carcinogenesis/genetics , Carcinogenesis/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Nucleus/metabolism , Cell Proliferation/genetics , Cytoplasm/metabolism , Epigenesis, Genetic , Female , Gene Silencing , Hexokinase/metabolism , Histones/metabolism , Humans , Lysine/metabolism , Male , Methylation , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Middle Aged , Models, Biological , Neoplasm Invasiveness , Neoplasm Metastasis , RNA, Long Noncoding/genetics , Transcription, Genetic , Up-Regulation/genetics , Urinary Bladder Neoplasms/pathologyABSTRACT
While hundreds of consistently altered autophagy-related genes (ARGs) have been identified in cancers, their prognostic value in bladder urothelial carcinoma (BUC) remains unclear. In the present study, we collected 232 ARGs from the Human Autophagy Database (HADb), and identified 37 differentially expressed ARGs in BUC based on The Cancer Genome Atlas (TCGA) database. Kaplan-Meier survival analysis based on the Gene Expression Profiling Interactive Analysis (GEPIA) database revealed that among the 37 differentially expressed ARGs, prolyl 4-hydroxylase, beta polypeptide (P4HB), and regulator of G protein signaling 19 (RGS19) were significantly negatively correlated with overall survival (OS) and disease-free survival (DFS). Overexpression of P4HB and RGS19 in BUC was further validated using independent data sets, including those from the Oncomine and Gene Expression Omnibus (GEO) databases. cBioPortal and UALCAN analyses indicated that altered P4HB and RGS19 mRNA expression was significantly associated with mutations and clinical characteristics (nodal metastasis and cancer stage). Moreover, co-expression network analysis and gene set enrichment analysis (GSEA) predicted that the potential functions of P4HB and RGS19 are involved in the endoplasmic reticulum (ER) stress response, cytokine-mediated signaling pathway and inflammatory response. More importantly, multivariate Cox proportional hazards regression analysis demonstrated that P4HB, but not RGS19, is an independent and unfavorable BUC biomarker based on clinical characteristics (age, gender, cancer stage, and pathological TNM stage). Finally, we validated that the mRNA and protein expression levels of P4HB were upregulated in four bladder cancer cell lines (T24, J82, EJ, and SW780) and found that knockdown of P4HB dramatically inhibited the invasion and proliferation of bladder cancer cells. In summary, our study screened ARGs and identified P4HB as a biomarker that can predict the progression and prognosis of BUC and may provide a better understanding of the autophagy regulatory mechanisms involved in BUC.
ABSTRACT
Recent findings have unraveled the critical functions of the long noncoding RNA (lncRNA) SNHG5 in human malignancies. Nevertheless, the role and mechanism of SNHG5 in clear cell renal cell carcinoma (ccRCC) are still elusive. In our study, substantially higher abundance of SNHG5 was observed in ccRCC specimens and cell lines, and increased SNHG5 expression was intimately correlated with tumor size, tumor-node-metastasis (TNM) stage, lymph node invasion, and distant metastases in patients with ccRCC. SNHG5 knockdown obviously suppressed the proliferative, migratory, and invasive capabilities of ccRCC cells, whereas SNHG5 overexpression induced the opposite effects. Mechanistically, SNHG5 activated the transcription of ZEB1, which exerts a pivotal role in modulation of epithelia-mesenchymal transition (EMT) and tumor metastasis. SNHG5 was then shown to act as an endogenous sponge for miR-205-5p, which targets ZEB1 in ccRCC. Moreover rescue experiments revealed that SNHG5 promotes ccRCC cell proliferation, migration, and invasion in a miR-205-5p-dependent manner. Additionally, in vivo assays further indicated that overexpression or silencing of SNHG5 in ccRCC cells promoted or suppressed the tumorigenesis and metastasis, respectively. Altogether, the present data provide the first evidence that the lncRNA SNHG5 has an oncogenic role in ccRCC through the SNHG5/miR-205-5p/ZEB1 signaling axis and represents a novel potential therapeutic regimen against ccRCC.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/pathology , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/pathology , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Zinc Finger E-box-Binding Homeobox 1/metabolism , Animals , Apoptosis , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Cell Proliferation , Epithelial-Mesenchymal Transition , Female , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Male , Mice , Mice, Nude , Middle Aged , Prognosis , Survival Rate , Tumor Cells, Cultured , Xenograft Model Antitumor Assays , Zinc Finger E-box-Binding Homeobox 1/geneticsABSTRACT
BACKGROUND: Long noncoding RNAs (lncRNAs) play important roles in competing endogenous RNA (ceRNA) networks involved in the development and progression of various cancers, including muscle-invasive bladder cancer (MIBC). PURPOSE: This study aims to construct the lncRNA-associated ceRNA network and identify lncRNA signatures correlated with the clinical features of MIBC tissue samples from The Cancer Genome Atlas (TGCA) database. METHODS: The differential expression profiles of MIBC associated lncRNAs, miRNAs and mRNAs were obtained from TCGA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the principal functions of significantly dysregulated mRNAs. The dysregulated lncRNA-associated ceRNA network of MIBC was constructed based on the bioinformatics data, and the correlations between lncRNA expression and clinical features were analyzed using a weighted gene coexpression network analysis (WGCNA). Six cancer specific lncRNAs from the ceRNA network were randomly selected to detect their expression in 32 paired MIBC tissue samples and 5 bladder cancer cell lines using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The ceRNA network was constructed with 30 lncRNAs, 13 miRNAs and 32 mRNAs. Seventeen lncRNAs in the ceRNA network correlated with certain clinical features, and only 1 lncRNA (MIR137HG) correlated with the overall survival (OS) of patients with MIBC (log-rank test P<0.05). GO and KEGG analyses revealed roles for the potential mRNA targets of MIR137HG in epithelial cell differentiation and the peroxisome proliferator-activated receptor (PPAR) and tumor necrosis factor (TNF) signaling pathways. The expression data from TCGA were highly consistent with the verification results of the MIBC tissue samples and bladder cancer cell lines. CONCLUSION: These findings improve our understanding of the regulatory mechanism of the lncRNA-miRNA-mRNA ceRNA network and reveal potential lncRNAs as prognostic biomarkers of MIBC.
ABSTRACT
Accumulating evidences suggest that circular RNAs play vital roles in human cancers. Previously, we found that circHIPK3 suppressed invasion of bladder cancer cells via sponging miR-558 and downregulating heparanase expression. In this study, we discovered that a circular RNA derived from NR3C1 (circNR3C1) was downregulated in bladder cancer tissues and cell lines according to RNA-Seq data and qRT-PCR analysis. Functionally, we found that overexpression of circNR3C1 could significantly inhibit cell cycle progression and proliferation of bladder cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistically, we demonstrated that circNR3C1 possessed four targeting sites of miR-27a-3p and could effectively sponge miR-27a-3p to suppress the expression of cyclin D1. Furthermore, we revealed that miR-27a-3p functioned as an oncogene through interacting with 5'UTR of cyclin D1 to enhance its expression, which led to promote cell cycle progression and proliferation in bladder cancer cells. Conclusively, our findings further confirm the hypothesis that circRNAs function as "microRNA sponges", and our data suggest that circNR3C1 and miR-27a-3p would be potential therapeutic targets for bladder cancer treatment.
Subject(s)
Cell Proliferation , Cyclin D1/metabolism , MicroRNAs/metabolism , RNA, Circular/metabolism , Urinary Bladder Neoplasms/metabolism , 5' Untranslated Regions , Animals , Binding Sites , Cell Cycle Checkpoints , Cell Line, Tumor , Cyclin D1/genetics , Down-Regulation , Gene Expression Regulation, Neoplastic , Humans , Mice, Nude , MicroRNAs/genetics , RNA, Circular/genetics , Signal Transduction , Tumor Burden , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: Gambogic acid (GA) is the main active ingredient of resin gamboges and possesses anti-cancer activity toward various human cancer cells. However, clinical application of GA has been limited by its poor aqueous solubility and dose-limiting toxicities. Cell-penetrating peptides (CPPs) are widely used to deliver anti-cancer drugs into cancer cells and to enhance the water solubility of drugs. PURPOSE: The object of this study was to synthesize peptide-drug conjugates in which the cell-penetrating peptide TAT (trans-activator of transcription) was conjugated to GA and evaluated the anti-cancer activity of this GA-CPP conjugate (GA-TAT) in EJ bladder cancer cells. METHODS: GA is built onto the TAT, and the GA-TAT conjugates are cleaved from the solid support and purified via HPLC. The equilibrium solubility of GA-TAT was measured using the shake-flask method. The effects of GA-TAT on EJ cell viability and proliferation were determined by MTT assay, Edu assay and colony formation assay, respectively. After treated with 1.0 µM GA-TAT for 24 h, the apoptosis rate of EJ cells were detected by Acridine orange/ethidium bromide (AO/EB) assay and flow cytometry assay. The proteins of caspase-3 (processing), caspase-9 (processing), Bcl-2 and Bax were analyzed by Western blotting, and the intracellular reactive oxygen species (ROS) production was evaluated by a reactive oxygen species assay. RESULTS: In contrast to free GA, the solubility of GA-TAT in water was significantly improved. Meanwhile, GA-TAT significantly increased EJ cellular uptake, toxicity and apoptosis. Mechanistic analysis revealed that GA-TAT enhanced the anti-cancer effect of GA against EJ cells through ROS-mediated apoptosis. The results were demonstrated that GA-TAT increased the ROS level in EJ cells, and N-acetyl-L-cysteine (NAC; a well-known ROS scavenger) inhibited GA-TAT-induced ROS generation and apoptosis. Additionally, GA-TAT activated caspase-3 and caspase-9 and down-regulated the Bcl-2/Bax ratio, but these effects were largely rescued by NAC. CONCLUSION: GA-TAT has outstanding potential for promoting tumor apoptosis and exhibits promise for use in bladder cancer therapy.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell-Penetrating Peptides/pharmacology , Reactive Oxygen Species/metabolism , Urinary Bladder Neoplasms/drug therapy , Xanthones/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Cell-Penetrating Peptides/chemical synthesis , Cell-Penetrating Peptides/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Reactive Oxygen Species/analysis , Structure-Activity Relationship , Tumor Cells, Cultured , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , Xanthones/chemistryABSTRACT
OBJECTIVE: To explore the mechanism of miR-124 inhibiting the proliferative activity of prostate cancer PC3 cells. METHODS: Luciferase reporter gene assay was used to examine the specific binding ability of miR-124 to PKM2 mRNA 3'-UTR. After miR-124 was transfected mimic to PC3 cells, the expression levels of PKM2 mRNA and protein were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot, respectively. The effects of miR-124 mimic and PKM2 siRNA on the proliferative activity of the PC3 cells were determined by MTT assay. RESULTS: The expressions of PKM2 mRNA and protein were upregulated (5.12 +/- 0.35) times and (4.05 +/- 0.20) times respectively in the PC3 cells as compared with those in the RWPE-1 cells (P < 0.05). Luciferase reporter gene assay demonstrated that miR-124 targeted PKM2 3'-UTR. At 24 hours after transfection with miR-124 mimic, the PKM2 protein expression in the PC3 cells was downregulated (0.16 +/- 0.04) times (P < 0.05), while the PKM2 mRNA level was not changed significantly (P > 0.05), as compared with the control group. MTT assay showed that both miRNA-124 mimic and PKM2 siRNA could inhibit the proliferation of the PC3 cells, but the former exhibited a greater inhibitory effect than the latter. After transfection with miR-124 mimic and PKM2 siRNA, the cell growth rates were (66.20 +/- 5.10)% vs (82.10 +/- 6.35)% at 24 hours (P < 0.05) and (49.34 +/- 2.37)% vs (70.10 +/- 5.80)% at 48 hours (P < 0.05). CONCLUSION: miR-124 can suppress the proliferation of PC3 cells by regulating the PKM2 gene.
Subject(s)
Carrier Proteins/genetics , Membrane Proteins/genetics , MicroRNAs/genetics , Prostatic Neoplasms/pathology , Thyroid Hormones/genetics , Carrier Proteins/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Humans , Male , Membrane Proteins/metabolism , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Thyroid Hormones/metabolism , Transfection , Thyroid Hormone-Binding ProteinsABSTRACT
Hypoxia has been involved in the development of tumor by regulating the expression of invasiveness-associated genes. However, the specific function of hypoxia in cancer cell invasion is still unclear. The aim of the present study was to determine the role of hypoxia in invasion of prostate cancer PC3 cells and to investigate the underlying mechanisms. We found that hypoxia significantly increased the invasive activity of PC3 cells, via up-regulation of the expression of hypoxia inducible factor 1α (HIF-1α) and the autocrine production of tumor necrosis factor α (TNF-α). More important, TNF-α cooperated with HIF-1α in promoting stabilization of Snail, a transcriptional repressor of E-cadherin expression, which lead to the up-regulation of invasiveness-associated genes MMP-9, fibronectin and vimentin. Snail silencing by specific siRNA significantly inhibited hypoxia-induced invasion of PC3 cells, indicating an essential role of Snail in conferring the malignant phenotype to cancer cells under hypoxic conditions. In conclusion, our data demonstrate that hypoxia promoted the invasiveness of prostate cancer PC3 cells via HIF-1α- and TNF-α-induced stabilization of Snail, suggesting a signaling mechanism involving HIF-1α/TNF-α/Snail that mediates invasiveness hypoxic tumor cells in the absence of neoangiogenesis.
Subject(s)
Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Prostate/metabolism , Transcription Factors/metabolism , Tumor Necrosis Factor-alpha/metabolism , Cadherins/genetics , Cadherins/metabolism , Cell Hypoxia/genetics , Cell Line, Tumor , Cell Migration Assays , Cell Movement , Cell Survival , Fibronectins/genetics , Fibronectins/metabolism , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Male , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Prostate/pathology , Protein Stability , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction , Snail Family Transcription Factors , Transcription Factors/antagonists & inhibitors , Transcription Factors/genetics , Tumor Necrosis Factor-alpha/genetics , Vimentin/genetics , Vimentin/metabolismABSTRACT
OBJECTIVE: To study the effect of silencing pyruvate kinase M2 (PKM2) on gambogic acid (GA)-induced apoptosis of human prostate cancer PC3 cells. METHODS: Three specific PKM2 siRNAs and one negative control siRNA (si-NC) were transfected into PC3 cells. The silencing effect of PKM2 siRNAs was determined by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot, and the effects of PKM2 siRNA on the vitality and apoptosis of GA-stimulated PC3 cells detected by MTT and AO/EB double staining, respectively. The mRNA and protein levels of c-myc and cyclin D1 were analyzed by qRT-PCR and Western blot, respectively. RESULTS: All the 3 PKM2 siRNAs effectively reduced the mRNA and protein expressions of PKM2, and PKM2 siRNA-1 exhibited the strongest silencing effect. At 24 h after transfection, the expression levels of PKM2 mRNA and protein were reduced by 70% and 85%, respectively (P < 0.05). Twenty-four hours of treatment with GA (0.5 micromol/L) following transfection with PKM2 siRNA-1 inhibited the vitality of the PC3 cells by 68%, increased their apoptosis, and significantly down-regulated the mRNA and protein levels of c-myc (50% and 35%) and cyclin D1 (60% and 20%) (P < 0.05). CONCLUSION: Inhibition of PKM2 sensitized PC3 cells to GA-induced apoptosis, suggesting that PKM2 may be a potential therapeutic target for sensitizing human prostate cancer to GA.
Subject(s)
Apoptosis/drug effects , Carrier Proteins/genetics , Membrane Proteins/genetics , Prostatic Neoplasms/genetics , RNA, Small Interfering , Thyroid Hormones/genetics , Xanthones/pharmacology , Carrier Proteins/metabolism , Cell Line, Tumor , Humans , Male , Membrane Proteins/metabolism , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , RNA Interference , Thyroid Hormones/metabolism , Thyroid Hormone-Binding ProteinsABSTRACT
The anti-tumor activity of curcumin against androgen-independent prostate cancer cells in vitro and the possible mechanism were investigated. After curcumin treatment, the effect of curcumin on the proliferation of prostate cancer PC-3 cells was assessed by CFSE staining. Flow cytometery (FCM) was performed to analyze the cell cycle and the induction of apoptosis of tumor cells. A luciferase reporter gene assay was used to determine the effects of curcumin on the activities of intracellular NF-κB and AP-1 signaling pathways. The results showed curcumin could effectively inhibit the proliferation of PC-3 cells in vitro (P<0.05). Cells were arrested at G(2)/M phase. After curcumin treatment, the percentage of apoptotic cells was significantly higher than in control group (P<0.05). The results of the luciferase assay revealed that curcumin selectively inhibited the activities of the NF-κB and AP-1 signaling pathways in PC-3 cells significantly. It was suggested that curcumin could exert anti-tumor activity against androgen-independent prostate cancer cells in vitro by inhibiting cellular proliferation and inducing apoptosis, which was probably contributed to the inhibition of transcription factors NF-κB and AP-1.
Subject(s)
Antineoplastic Agents/pharmacology , Curcumin/pharmacology , NF-kappa B/antagonists & inhibitors , Prostatic Neoplasms/drug therapy , Signal Transduction/drug effects , Transcription Factor AP-1/antagonists & inhibitors , Androgens/metabolism , Cell Line, Tumor , Humans , Male , NF-kappa B/metabolism , Transcription Factor AP-1/metabolismABSTRACT
The anti-tumor activity of curcumin against androgen-independent prostate cancer cells in vitro and the possible mechanism were investigated.After curcumin treatment,the effect of curcumin on the proliferation of prostate cancer PC-3 cells was assessed by CFSE staining.Flow cytometery (FCM) was performed to analyze the cell cycle and the induction of apoptosis of tumor cells.A luciferase reporter gene assay was used to determine the effects of curcumin on the activities of intracellular NF-κB and AP-1 signaling pathways.The results showed curcumin could effectively inhibit the proliferation of PC-3 cells in vitro (P<0.05).Cells were arrested at G2/M phase.After curcumin treatment,the percentage of apoptotic cells was significantly higher than in control group (P<0.05).The resuits of the luciferase assay revealed that curcumin selectively inhibited the activities of the NF-κB and AP-1 signaling pathways in PC-3 cells significantly.It was suggested that curcumin could exert anti-tumor activity against androgen-independent prostate cancer cells in vitro by inhibiting cellular proliferation and inducing apoptosis,which was probably contributed to the inhibition of transcription factors NF-κB and AP- 1.
ABSTRACT
OBJECTIVE: To compare the effect of Acanthopanacis senticosi injection, theophylline and caffeine on human sperm mobility in vitro. METHODS: We incubated the sperm aseptically obtained by masturbation from 12 asthenospermia men and treated by swim-up technique in Acanthopanacis senticosi injection (10 g/L), theophylline (3 mmol/L) and caffeine (7 mmol/L) respectively, and detected various sperm parameters with the computer-assisted sperm analysis (CASA) system at 0 h, 1 h and 3 h. RESULTS: Acanthopanacis senticosi injection significantly increased sperm motility, the percentage of progressive motile sperm, straight line velocity (VSL) and curvilinear velocity (VCL) as compared with theophylline and caffeine (P < 0.05). CONCLUSION: Acanthopanacis senticosi injection can activate the mobility of human sperm in vitro.
Subject(s)
Caffeine/pharmacology , Drugs, Chinese Herbal/pharmacology , Sperm Motility/drug effects , Theophylline/pharmacology , Eleutherococcus/chemistry , Humans , In Vitro Techniques , MaleABSTRACT
OBJECTIVE: To investigate the clinical efficacy, surgical indications and postoperative complications of mid urethral sling procedures in treatment of female stress urinary incontinence. METHODS: A multicenter clinical trial was conducted from April 2002 to April 2008 in five hospitals, 304 cases of genuine stress urinary incontinence and 8 cases of mixed incontinence were included. TVT procedures were carried out in 134 patients, TVTO procedures in 167 patients, Monarc procedures in 11 patients. Perioperative evaluations included: operating time, bleeding volume, and perioperative complications. Operative efficacy was classified into three categories: cure, improved and failure and evaluated before discharge, 3 months after surgery and then every year. RESULTS: TVT group had longer operating time [(18.5 + or - 9.6) min] and more bleeding volume [(32.2 + or - 12.6) ml] than those in TVTO group [(11.5 + or - 3.1) min, (12.8 + or - 8.5) ml] and in Monarc group [(11.1 + or - 2.6) min, (12.3 + or - 3.5) ml] with P < 0.05. Monarc and TVTO procedures had higher cure rates and improve rates comparing with TVT, but the differences were of no significance. The cure rate (95.7%) in patients with genuine stress incontinence were significantly higher than that in patients with mixed incontinence (37.5%). No significant differences of total intra- and postoperative complications were noted for all of the three procedures. However, bladder injury tended to occur in TVT group and obturator nerve injury and vaginal injury tended to occur in TVTO group. Transient voiding dysfunction and urinary retention were the most common complications. CONCLUSIONS: Mid urethral sling procedures have excellent clinical outcomes in the treatment of female stress urinary incontinence.
Subject(s)
Suburethral Slings , Urinary Incontinence, Stress/surgery , Female , Follow-Up Studies , Humans , Middle Aged , Treatment OutcomeABSTRACT
OBJECTIVE: To study the psychological factors and erectile function in patients with refractory chronic prostatitis. METHODS: We obtained and compared the scores on the NIH scales of chronic prostatitis symptoms, anxiety, depression and erectile function among 232 refractory and medical chronic prostatitis patients who had never received any psychotherapy. RESULTS: No significant differences were observed in the scores on chronic prostatitis symptoms between the refractory and the medical chronic prostatitis groups, while the scores on anxiety and depression were significantly higher and that on erectile function significantly lower in the refractory than in the medical group (P < 0.01), with a negative correlation between the scores on the former two items and that on the latter. CONCLUSION: Obvious psychological factors exist in patients with refractory chronic prostatitis, which may affect their erectile function.