MicroRNA-488 inhibits proliferation and glycolysis in human prostate cancer cells by regulating PFKFB3.

Prostate cancer (PCa) remains the second leading cause of cancer-related death among men in the United States, and its molecular mechanism remains to be elucidated. Recent studies have suggested that microRNAs may play an important role in cancer development and progression. By analyzing the Gene Expression Omnibus dataset, we found lower expression for miR-488 in PCa than in normal tissues. Moreover, CCK-8, EdU, glucose uptake, and lactate secrete assays revealed that overexpression of miR-488 in PCa cell lines PC3 and DU145 resulted in inhibition of proliferation and glycolysis. In contrast, downregulation of miR-488 expression promoted proliferation and glycolysis in PCa cells. Using a bioinformatic approach and dual-luciferase reporter assays, we identified 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform3 (PFKFB3), as a direct target of miR-488. Inhibition of PFKFB3 also suppressed PCa cell glycolysis and proliferation. Our study suggests that miR-488 inhibits PCa cell proliferation and glycolysis by targeting PFKFB3, and thus, miR-488 may be a novel therapeutic candidate for PCa.

Exenatide inhibits the growth of endometrial cancer Ishikawa xenografts in nude mice.

Studies have showed that diabetes is one of the high risk factors of endometrial cancer; however, no reports describe the anti- or pro-cancer effect of a new kind of anti-diabetes drug, glucagon-like peptide-1 receptor agonist exenatide (exendin-4), on endometrial cancer. To investigate whether exenatide promotes or inhibits the growth of endometrial cancer, we used the subcutaneous human endometrial cancer cell Ishikawa xenografts in nude mouse model, and divided them into control group and exenatide-treated group. The tumor growth rate in exenatide group was slower than that in control group, and the apoptosis rate of exenatide group was higher than that in control group. In vitro, exendin-4 also attenuated Ishikawa cell viability and clone formation rate, but promoted cell apoptosis. There was an increase of phosphorylated-AMPK protein, a decrease of phosphorylated-mTOR protein both in vivo and in vitro after exenatide or exendin-4 treatment. Moreover, when treated with exendin-4 plus AICAR, an AMPK activator, cell apoptosis increased with higher ratio of phosphorylayed-AMPK/AMPK, lower ratio of phosphorylated-mTOR/mTOR and higher expression of cleaved caspase-3 than those in exendin-4 alone group, and the results were the opposite when treated with exendin-4 plus compound C, an AMPK inhibitor. Our results suggest that exenatide could attenuate the growth of endometrial cancer Ishikawa xenografts in nude mice, and AMPK may be the target of the mechanism.

Laparoscopic radical prostatectomy plus extended lymph nodes dissection for cases with non-extra node metastatic prostate cancer: 5-year experience in a single Chinese institution.

OBJECTIVE: To investigate the functional and oncologic outcomes of patients with locally advanced or lymph node metastatic prostate cancer (PCa) treated by laparoscopic radical prostatectomy (LRP) in a single Chinese institution. METHODS: From June 2004 to June 2011, a total of 152 cases including 105 locally advanced PCa and 47 lymph node metastatic PCa who were treated by LRP with extended lymph node dissection (ePLND) were enrolled in this study. Surgical records, urinary continence, complications, and oncologic outcomes were presented. RESULTS: The mean operation time and bleeding were 240 min and 110 ml, respectively. After 12-87 months (median 48 m) of follow-up, 91.4 and 94.7 % of the patients were urinary continence at 6 and 12 m, respectively. Eighty biochemical recurrent diseases were observed. The 3- and 5-year biochemical progression-free survival rates were 59.2 and 47.3 %, respectively. Multivariate analysis showed that Gleason score (HR: 1.66, 95 % CI: 1.05-2.64, P = 0.031), pathological stage (HR: 1.64, 95 % CI: 1.2-2.23, P = 0.002), and surgical margin status (HR: 1.75, 95 % CI: 1.04-2.95, P = 0.035) were independent predictive factors for subsequent biochemical relapse. The 3- and 5-year overall and cancer-specific survival rates were 90.2, 86.0 and 95.8, 92.3 %, respectively. There were no significant differences in biochemical recurrence-free (42.6 vs. 49.5 %, P = 0.491), overall (83.4 vs. 87.3 % P = 0.503), and cancer-specific survival rates (92.3 vs. 94.9 %, P = 0.801) between lymph node-positive and -negative PCa. CONCLUSION: With favorable functional and oncologic outcomes in this cohort of 152 patients, we concluded that LRP plus ePLND is feasible for patients with locally advanced non-extra node metastatic PCa.

Docetaxel loaded oleic acid-coated hydroxyapatite nanoparticles enhance the docetaxel-induced apoptosis through activation of caspase-2 in androgen independent prostate cancer cells.

Docetaxel (Dtxl) remains the preferred choice of improving the survival of patients with hormone refractory prostate cancer (HRPC), but many patients suffer from modest drug response and significant toxicity. In the present study, we investigated the efficiency of novel Dtxl loaded-[1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-carboxy(polyethylene glycol)]2000 (DSPE-PEG-COOH) stabilized-oleic acid (OA) coated hydroxyapatite (HA) nanoparticles (Dtxl-NPs) and gained insights into the molecular mechanism of the apoptosis induced by these novel Dtxl-loaded nanoparticles. The drug encapsulation efficiency of Dtxl was 83.6% and the sustained drug release was observed over 30days. The Dtxl-NPs exhibited significantly more cytotoxicity in both prostate cancer cell lines (PC3 and DU145) compared with Dtxl in vitro and increased the Dtxl-induced apoptosis in the PC3 cells. Cell cycle analysis showed that the PC3 cells treated with Dtxl-NPs exhibited significant arrest in the G2-M phase but a higher sub-G(0)/G(1) population when compared with Dtxl. The enhanced apoptosis induced by Dtxl-NPs in the PC3 cells was associated with the changes in mitochondrial membrane potential (MMP) and seemed to involve the activation of caspase-2. The kinetic studies of caspases demonstrated an early activation of caspase-2 in Dtxl-NPs-induced apoptosis in PC3 cells, which differs from Dtxl-induced apoptosis. The inhibition of caspase-2 activation by small interfering RNA (siRNA) knockdown resulted in the significant inhibition of Dtxl-NPs-induced disruption of MMP and Dtxl-NPs-induced apoptosis, indicating that the activation of caspase-2 was the critical event before the mitochondrial depolarization in the PC3 cells. Our findings showed that nanoparticles, more than simple drug carriers, may play an active role in mediating the biological effects.

Proteomic analysis of rat penile tissue in a model of erectile dysfunction after radical prostatectomy.

OBJECTIVE: To identify differential protein expression in penile tissue in a rat model of erectile dysfunction (ED) at an early stage after bilateral cavernosal nerve (CN) neurectomy, using proteomic techniques. MATERIALS AND METHODS: Twelve male adult Sprague-Dawley rats were randomly divided into two equal groups, one having bilateral CN resection and one a control group. The penises were harvested 7 days after CN resection. Total protein was separated into >1250 protein spots by two-dimensional electrophoresis using pH 3-10 nonlinear immobilized pH gradient strips. Differential expression of proteins was analysed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and database searching. RESULTS: Thirty-two proteins were significantly changed in the denervated penis, of which 25 (including nine up-regulated and 16 down-regulated) with cytoskeletal functions, and pathophysiological functions related to energy metabolism and oxidative stress, were identified. Examples include transgelin, creatine kinase B, annexin-1 and galactin-7. CONCLUSIONS: The expression of several important proteins participating in pathophysiological processes of penile tissue are changed early after bilateral CN neurectomy. These changes might give new insights into the cellular and molecular mechanisms involved in neurogenic ED development, and indicate potential therapeutic targets.