Cognitive fusion-targeted biopsy versus transrectal ultrasonography-guided systematic biopsy: comparison and analysis of the risk of Gleason score upgrading.

PURPOSE: The aim of this study is to assess the precision of the Gleason score (GS) obtained through cognitive fusion-targeted biopsy (COG-TB) in comparison to transrectal ultrasonography-guided systematic biopsy (TRUS-SB), and to identify factors that can predict Gleason score upgrading (GSU) in a cohort of Chinese patients. METHODS: A final enrollment of 245 patients was recorded. Between 2020 and 2022, 132 patients underwent TRUS-SB, and 113 patients underwent COG-TB. The Chi-square test was performed to analyze the variation in downgrading, concordance, and upgrading between TRUS-SB and COG-TB. Multivariable analyses were performed to seek factors predicting Gleason score upgrading. Finally, a model which utilizes multivariable logistic regression was developed to predict the likelihood of GSU. RESULTS: The concordance for TRUS-SB and COG-TB were 42.4% and 65.5%, respectively. TRUS-SB and COG-TB exhibited notable disparities in downgrading, concordance, and upgrading. Age, prostate volume, body mass index (BMI), and the biopsy modality were significant predictive factors. CONCLUSION: COG-TB can significantly increase concordance with final histopathology. Age, prostate volume, BMI, and the biopsy modality were predictive factors of GSU.

Association of lower urinary tract symptoms and geriatric nutritional risk index in men: a cross-sectional study based on NHANES.

Background: Despite previous literature exploring the factors influencing lower urinary tract symptoms (LUTS), few studies have examined the relationship between nutritional status and LUTS. Objectives: The objective of this research was to evaluate the relationship between LUTS and Geriatric Nutritional Risk Index (GNRI) in middle-aged and older men. Methods: We included 2,607 men in the NHANES 2005-2006 and 2007-2008 cycles for cross-sectional analysis. We screened for LUTS based on four specific questions on the relevant questionnaire. We calculated GNRI according to the relevant calculation formula and included other covariates. Multivariate logistic analysis using GNRI as the principal independent variable and adjusting for other covariates were used to determine the association with LUTS, nocturia, and daytime LUTS. Results: According to the responses to the questionnaire, out of 2,607 eligible participants, 471 had LUTS, 906 had nocturia, and 819 had daytime LUTS. In the unadjusted regression model, LUTS (OR = 0.93, 95% CI = 0.91-0.96, p < 0.001), nocturia (OR = 0.90, 95% CI = 0.88-0.93, p < 0.001), and daytime LUTS (OR = 0.96, 95% CI = 0.94-0.99, p = 0.002) were significantly negatively associated with GNRI. After adjustment by adding covariates, LUTS (OR = 0.97,95% CI =0.94-0.99, p = 0.026) and nocturia (OR = 0.94, 95% CI =0.91-0.93, p < 0.001) were significantly negatively associated with GNRI. Conclusion: Low GNRI was associated with the development of LUTS. In the prevention and treatment of LUTS, urologists should consider the impact of nutritional status on LUTS, and interventions for nutritional status may prevent and improve LUTS.

Berberine inhibits the migration and invasion of T24 bladder cancer cells via reducing the expression of heparanase.

Berberine, a quaternary amine and isoquinoline alkaloid, has been proposed to have antimetastatic effects on many types of tumor cells; however, its exact inhibitory mechanisms with bladder cancer cells remain unclear. We used berberine and siRNA technology to interfere the expression of heparanase in bladder cancer T24 cells, detected the expression of heparanase mRNA and protein by reverse transcription PCR and Western blot respectively, and investigated their effects on the migration and invasion of T24 bladder cancer cells using transwell chamber. Our results showed that both mRNA and protein of heparanase were highly expressed in human bladder cancer T24 cells and markedly downregulated by both heparanase-specific siRNA (hpa-siRNA) and berberine. The tumor cell migration assay indicated that transfection of hpa-siRNA and treatment with berberine both attenuated the migration and invasion of T24 cells. Therefore, berberine inhibits the metastasis and invasion of bladder cancer cell, possibly via blocking the heparanase expression and thus may be used clinically to reduce the recurrence of bladder cancer.

Comparing histology between prostate cognitive fusion targeted biopsy and radical prostatectomy: exploring risk factors of Gleason score upgrading in Chinese patients.

PURPOSE: To explore and identify the relevant clinical and pathological predictors leading to biopsy Gleason score upgrading (GSU) in cognitive fusion targeted biopsy (COG-TB) in Chinese patients. METHODS: Clinical and pathological information of 496 patients who underwent COG-TB and radical prostatectomy (RP) in our hospital from January 2020 to September 2023 were retrospectively compiled and analyzed. In this study, we screened valuable predictors through univariable and multivariable logistic regression analyses and then constructed predictive models. We draw nomograms to visualize the predictive models. In addition, the discriminatory power of the model was assessed using receiver operating characteristic (ROC) curves. Finally, calibration curves and decision curve analysis (DCA) were used to evaluate the predictive power of the model and the net benefits it could deliver. RESULTS: Out of the 496 patients eligible for the study, 279 had a consistent Gleason score (GS) on biopsy and postoperative GS, 191 experienced GSU, and 26 experienced downgrading. Significant associations for GSU were identified for five risk factors through multivariable logistic regression analyses, which included age, prostate volume, BMI, tumor percentage in biopsy tissue, and tumor location. Our model had excellent discriminatory power through ROC analysis. Calibration curves and DCA showed that our model was well calibrated and provided certain benefits for patient treatment decisions. CONCLUSION: Age, prostate volume, BMI, tumor percentage in biopsy tissue, and tumor location are risk indicators for predicting GSU in COG-TB. Our prediction model is more suitable for Chinese patients and can assist in accurately evaluating biopsy GS and developing effective treatment plans.

Lack of association between hOGG1 Ser326Cys polymorphism and the risk of bladder cancer: a meta-analysis.

OBJECTIVE: In some but not all studies, hOGG1 Ser326Cys polymorphism has been reported to contribute to the risk of bladder cancer. To determine whether there is a significant association of hOGG1 Ser326Cys polymorphism with the susceptibility for bladder cancer, we performed a comprehensive meta-analysis. METHODS: The electronic PubMed, Medline and Springer databases were searched for publications on the association between hOGG1 Ser326Cys polymorphism and bladder cancer through to May 20, 2011. Seven case-control studies were identified, including 2,474 cases and 2,408 controls. From these identified publications, crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of association using fixed- or random-effects models. Two investigators each extracted data and conducted the analysis independently. RESULTS: Overall, no significant associations were found between hOGG1 Ser326Cys polymorphism and bladder cancer in codominant models (GG vs. CC: OR 1.11, 95% CI 0.74-1.66, p = 0.63; GC vs. CC: OR 1.07, 95% CI 0.80-1.41, p = 0.65). Similarly, no significant associations with bladder cancer were observed in the recessive model (GG vs. GC+CC: OR 1.05, 95% CI 0.65-1.70, p = 0.85), dominant model (GG+GC vs. CC: OR 1.07, 95% CI 0.87-1.32, p = 0.53) and allele model (G vs. C: OR 1.06, 95% CI 0.90-1.26, p = 0.49). In the stratified analyses by ethnicity, control sources, pathology, Hardy-Weinberg equilibrium, significant associations were still not observed. CONCLUSIONS: The overall current literature on hOGG1 Ser326Cys polymorphism and the risk of bladder cancer suggests no statistically significant association between the two. Additional primary studies may be necessary to provide evidence of any significant association between this specific polymorphism and bladder cancer.

Multi-Omics Analysis of the Expression and Prognosis for FKBP Gene Family in Renal Cancer.

BACKGROUND: The FK506-binding protein (FKBP) is a family of intracellular receptors that can bind specifically to the immunosuppressant FK506 and rapamycin. Although FKBPs play crucial roles in biological processes and carcinogenesis, their prognostic value and molecular mechanism in clear cell renal cell carcinoma (ccRCC) remain unclear. METHODS: Using pan-cancer data from The Cancer Genome Atlas (TCGA) and public databases, we analyzed the expression and correlation of FKBPs in 33 tumor types. Survival and Cox regression analyses were employed to explore the prognostic value of FKBPs. The relationship with tumor microenvironment and stemness indices was taken into account to evaluate the function of FKBPs. We constructed a risk score model to predict the prognosis of patients with ccRCC. The receiver operating characteristic (ROC) curve was performed to further test the prognostic ability of our model. Nomogram, joint effects analysis, and clinical relevance were performed to assist the clinician. Gene set enrichment analysis (GSEA) and cell line experiments were performed to investigate the function and molecular mechanisms of FKBPs in patients with ccRCC. Paired clinical specimens and multi-omics analysis were used to further validate and explore the factors affecting gene expression in ccRCC patients. RESULTS: The expression levels of FKBP10 and FKBP11 were higher in ccRCC tissues than in normal tissues. The alteration in expression may be because of the degree of DNA methylation. Increased expression levels of FKBP10 and FKBP11 were associated with worse overall survival (OS). More importantly, GSEA revealed that FKBP10 is mainly involved in cell metabolism and autophagy, whereas FKBP11 is mainly associated with immune-related biological processes and autophagy. Cell Counting Kit 8 (CCK-8) and Transwell assays revealed that knockdown of FKBP10 and FKBP11 inhibits proliferation, migration, and invasion of the ccRCC cell line. CONCLUSION: FKBP10 and FKBP11 play important roles in ccRCC phenotypes and are potential prognostic markers as well as new therapeutic targets for patients with ccRCC.

Effect of Deep Brain Stimulation on Female Parkinsonian Patients with Lower Urinary Tract Symptoms.

PURPOSE: This study aimed to investigate the characteristics of urodynamics in female parkinsonian patients with lower urinary tract symptoms (LUTS) and evaluate the outcomes of deep brain stimulation (DBS) based on overactive bladder (OAB) scores and quality of life (QOL) scores. PATIENTS AND METHODS: Urodynamic assessment was performed in 20 female parkinsonian patients with LUTS. OAB scores and QOL scores were collected before and 6 months after DBS treatment (The target of DBS is STN). We evaluated the related factors affecting QOL score and also the changes in QOL score after DBS treatment. RESULTS: The mean age of 20 patients was 60.6±6.3 years, with 65% of patients identified with OAB in urodynamic studies. The mean OAB total score and QOL score at baseline were 7.3±3.7 and 5.0±1.1, respectively. Four items in the OAB score were found to be independent factors and they influenced the baseline QOL scores. Six months after DBS treatment, the OAB total score and the QOL score were significantly decreased (3.7±3.2 (p = 0.002) and 3.4±1.4 (p < 0.001), respectively). Improvements in OAB item 2 (nocturia) and item 3 (urgency) scores were found to be independent factors, which had an influence on the improvement in QOL scores from multivariate analysis. Improvement of OAB item 2 (nocturia) exhibited the greatest influence on improvement in the QOL score. After DBS treatment, 40% of the patients showed significant improvement in urination symptoms (≥2 points reduction in QOL score), 30% of the patients showed mild improvement (1 point reduction in QOL score), and 30% patients showed no improvement (no change in QOL score). No patients exhibited worsening urination symptoms. CONCLUSION: Most parkinsonian female patients with lower urinary tract symptoms were diagnosed with OAB. DBS treatment improved OAB symptoms. Improvement of nocturia and urgency positively impacts the QOL of female parkinsonian patients.

Clinical observation on 2 micron laser for non-muscle-invasive bladder tumor treatment: single-center experience.

OBJECTIVES: To evaluate the efficacy and safety of 2 micron continuous wave laser resection of non-muscle-invasive bladder tumor (NMIBT) compared with holmium laser resection of bladder tumor (HoLRBT) and standard transurethral resection of bladder tumor (TURBT). METHODS: Since April 2006 to August 2007, 97 patients with NMIBT were retrospectively collected in this study. All of them were classified into 3 groups, which were treated with 2 micron continuous wave laser resection, holmium laser resection and TURBT, respectively. The preoperative, intraoperative and postoperative clinical data were recorded and compared using SAS 6.12 statistical software. RESULTS: There were no differences with the preoperative characteristics among the three groups, except the diameter of the tumors. The maximum diameter of the tumors in 2 micron laser group was larger than the other two groups (P < 0.05). Two micron laser group was associated with less hemoglobin decrease compared with TURBT group (P < 0.05). All of the patients were followed and the recurrence rate of the three groups indicated no statistical significance (P > 0.05). CONCLUSIONS: In conclusion, 2 micron continuous wave laser resection of non-muscle-invasive bladder tumor is a safe and reliable treatment. With the distinguished hemostasis, it is an available optional treatment.

[Proportion of intermediate epithelial cells and human prostate cancer].

OBJECTIVE: To study the different proportions of intermediate epithelial cells in human prostate cancer tissue and their clinical significance. METHODS: 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. RESULTS: 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). CONCLUSION: A higher proportion of intermediate epithelial cells may lead to increased invasiveness and metastasis of human prostate cancer.

Prognostic Significance of Cyclin D1 Expression in Renal Cell Carcinoma: a Systematic Review and Meta-analysis.

Previous studies indicated that cyclin D1 shown the potential as a tumor biomarker. However, the prognostic value of cyclin D1 in renal cell carcinoma (RCC) remains controversial. This study investigated the correlation of cyclin D1 expression with the prognostic and clinicopathological features in RCC patients. We systematically searched the database of PubMed, Embase, Cochrane, and Web of Science updated on November 26, 2017. Eighteen studies with 2282 patients satisfied the inclusion criteria. Results demonstrated that cyclin D1 overexpression in RCC showed significant favorable prognostic impact on disease-free survival (DFS) (HR 0.57, 95% CI: 0.43-0.74) and disease-specific survival (DSS) (HR 0.59, 95% CI 0.41-0.85) without significant heterogeneity. In subgroup of clear cell RCC, the prognostic effect on DFS was robust and the pooled HR was 0.39 (95% CI: 0.27-0.57). However, no association between overall survival (OS) and cyclin D1 expression was observed. Stratified analysis in DFS studies by sample size, staining patterns race and metastasis status showed similar results. Otherwise, cyclin D1 overexpression predicted a reduced prevalence of high TNM stage (T3 + T4) (OR 0.63, 95% CI: 0.40-0.99), high-grade tumor (G3 + G4) (OR 0.51, 95% CI: 0.31-0.81) and large tumor size (OR 0.35, 95% CI: 0.19-0.62). Our meta-analysis indicated that cyclin D1 overexpression could predict the favorable prognosis in patients with RCC.

Production of bioethanol from unwashed-pretreated rapeseed straw at high solid loading.

Reduction in water consumption and increase in ethanol concentration are two main challenges for bioethanol production from lignocellulosic materials. To address the two challenges, the aim of this work was to study the production of bioethanol from unwashed-pretreated rapeseed straw (RS) at high solid loading. RS pretreated with 1% (w w-1) H2SO4 at 160 °C for 10 min resulted in excellent digestibility and fermentability of pretreated RS. The unwashed-pretreated RS was subjected to presaccharification and fed-batch simultaneous saccharification and fermentation (P-FB-SSF) at a final solid loading of 22% (w w-1). Ethanol concentration and ethanol yield of 53.1 g L-1 (equivalent to 4.1% (w w-1) based on fermentation slurry) and 72.4% were obtained, respectively. In total, 92.1 g water g-1 ethanol was consumed, a much smaller amount than that observed with washing after pretreatment or fermentation performed at lower solid loading.

Chimeric molecules facilitate the degradation of androgen receptors and repress the growth of LNCaP cells.

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.

[Targeted degradation of androgen receptors in androgen-independent prostate cancer cells: an experimental study].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Ethanol extract of Patrinia scabiosaefolia induces the death of human renal cell carcinoma 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions.

Recently, natural plant extracts have shown tremendous potential as novel antitumor drugs. Patrinia scabiosaefolia, a traditional prescription for inflammatory diseases, has been reported to effectively suppress various types of cancers. However, the mechanisms underlying its antitumor properties remain elusive. In the present study, we investigated the antitumor effects of an ethanol extract of Patrinia scabiosaefolia (EPS) on human renal cell carcinoma 786-O cells. After 24 h of incubation with EPS, the cell viability and colony number of 786-O cells were significantly decreased in a concentration-dependent manner as compared to the control group as determined by MTT and colony formation assays, respectively. The necrotic rate and apoptotic rate in the EPS exposure group were significantly higher than these rates noted in the control group as revealed by LDH release assay and Hoechst 33342/ PI double staining, respectively. At the concentration of 1.0 mg/ml, the necrotic and apoptotic rates reached 41.7±6.6 and 7.8±1.4%, respectively (P<0.01). However, the fluorescence intensity of intracellular calcium concentration ([Ca2+]i) was markedly elevated from 0.029±0.0007 to 0.060±0.003 (P<0.001) after the intervention of EPS. Moreover, the fluorescence intensity of intracellular ROS in the EPS exposure group was significantly higher (0.074±0.005) compared to that observed in the control group (0.033±0.001, P<0.001), which was partly attenuated by the specific antioxidant N-acetylcysteine (NAC). Furthermore, our results demonstrated that EPS significantly downregulated the expression of SIRT-1 and obviously induced the dephosphorylation of mTOR. Moreover, combined treatment with the SIRT-1 inhibitor nicotinamide and EPS was able to significantly enhance the induction of necrosis and reduction in cell viability of 786-O cells noted following treatment with EPS alone. In summary, we conclude that EPS induced the death of 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions, which provide novel insight into the application of natural plant extracts for the treatment of cancers.

Cytoplasmic expression of pontin in renal cell carcinoma correlates with tumor invasion, metastasis and patients' survival.

Renal cell carcinoma (RCC) is the most lethal of all genitourinary malignancies. Distant metastasis represents the major cause of death in patients with RCC. Recent studies have implicated the AAA+ ATPase pontin in many cellular activities that are highly relevant to carcinogenesis. In this study, we demonstrate for the first time that pontin was up-regulated in RCC, and plays a previously unknown pro-invasive role in the metastatic progression of RCC through epithelial-to-mesenchymal transition (EMT) pathway. 28 pairs of freshly frozen clear cell RCC samples and the matched normal renal tissues analyzed by quantitative RT-PCR and western blotting demonstrated that pontin was up-regulated in clear cell RCC tissues than in normal renal tissues. In addition, immunohistochemistry was used to evaluate subcellular pontin expression in 95 RCC patients, and found that overexpression of pontin in cytoplasm positively correlated with the metastatic features, predicting unfavorable outcomes of RCC patients. Furthermore, in vitro experiments show pontin was predominantly expressed in cytoplasm of RCC cell lines, and a significant suppression of cell migration and invasion in pontin siRNA treated RCC cell lines was observed. Mechanistic studies show that pontin depletion up-regulated the E-cadherin protein and down-regulated vimentin protein, and decreased nuclear ß-catenin expression, suggesting the involvement of EMT in pontin induced metastatic progression. Together, our data suggest pontin as a potential prognostic biomarker in RCC, and provide new promising therapeutic targets for clinical intervention of kidney cancers.

Correction: A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine.

Correction for 'A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine' by Shenghua Gu et al., Mol. BioSyst., 2015, DOI: .

A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine.

Clinical and animal studies demonstrated that orally administered berberine had a distinct lipid-lowering effect. However, pharmacokinetic studies showed that berberine was poorly absorbed into the body so the levels of berberine in the blood and target tissues were far below the effective concentrations revealed. To probe the underlying mechanism, the effect of berberine on the biological system was studied on a high-fat-diet-induced hamster hyperlipidemia model. Our results showed that intragastrically-administered berberine was poorly absorbed into circulation and most berberine accumulated in gut content. Although the bioavailability of intragastrically administered berberine was much lower than that of intraperitoneally administered berberine, it had a stronger lipid-lowing effect, indicating that the gastrointestinal tract is a potential target for the hypolipidemic effect of berberine. A metabolomic study on both serum and gut content showed that orally administered berberine significantly regulated molecules involved in lipid metabolism, and increased the generation of bile acids in the hyperlipidemic model. DNA analysis revealed that the orally administered berberine modulated the gut microbiota, and berberine showed a significant inhibition of the 7α-dehydroxylation conversion of cholic acid to deoxycholic acid, indicating a decreased elimination of bile acids in the gut. However, in model hamsters, elevated bile acids failed to downregulate the expression and function of CYP7A1 in a negative feedback loop. It was suggested that the hypocholesterolemic effect of orally administered berberine involves modulating the turnover of bile acids and the farnesoid X receptor signal pathway.

Nitidine chloride induces apoptosis and inhibits tumor cell proliferation via suppressing ERK signaling pathway in renal cancer.

Nitidine chloride (NC), a natural bioactive alkaloid derived from Zanthoxylum nitidum (Roxb) DC, has been shown to have inhibitory effects on various tumors. However, whether NC could exert anti-cancer activity and the underlying mechanisms have not been elucidated in renal cancer cells. In this study, we demonstrated the growth inhibitory and pro-apoptotic effects of NC on renal cancer cells both in vitro and in vivo. With cell viability and flow cytometric apoptosis assays, we found that NC potently suppressed the growth of 786-O and A498 cells in a time- and dose- dependent manner. Consistently, the xenograft model performed in nude mice exhibited reduced tumor growth with NC treatment. Mechanically, we presented that NC significantly decreased phosphorylation of ERK and Akt, accompanied by up-regulation of P53, Bax, cleavage caspase-3 and cleavage PARP, downregulation of Bcl-2, caspase-3 and PARP. Furthermore, a specific MEK inhibitor, PD98059, could potentiate the pro-apoptotic effects of NC, which indicated that NC might trigger apoptosis in renal cancer cells partly via inhibition of ERK activity. Taken together, our results imply that NC could be developed as a potential anticancer agent to renal cancer and worthy of further studies.

Nitidine chloride inhibits renal cancer cell metastasis via suppressing AKT signaling pathway.

Nitidine Chloride (NC) has been shown to have anti-cancer effects on various tumors. However, whether NC could exert anti-metastasis activity in renal cancer cells and the underlying mechanisms have not been elucidated. In this work, our data demonstrated the anti-metastasis effects of NC on renal cancer cells in vitro. With scratch assay and transwell assays, we found that NC potently suppressed the migration and invasion of 786-O and A498 cells. Mechanistically, we presented that NC significantly decreased phosphorylation of AKT, accompanied by down-regulation of MMP-2 and MMP-9. Furthermore, a specific AKT inhibitor, LY294002, could enhance the anti-metastasis effects of NC, which indicated that NC suppressed metastasis of renal cancer cells partly via inhibition of AKT activity. Taken together, our results imply that NC can be developed as a potential anti-metastasis agent to renal cancer.