PDCD4 suppresses proliferation, migration, and invasion of endometrial cells by inhibiting autophagy and NF-κB/MMP2/MMP9 signal pathway.

Endometriosis (EM) is a kind of estrogen-dependent disease in reproductive-age women. Ovarian EM is the most common type. Although EM is a benign disease, it shares many similar features with cancers. Programmed cell death 4 (PDCD4), a newly identified tumor suppressor, plays an important role in inhibiting tumorigenesis and tumor progression at the transcriptional and translational levels. To explore the roles of PDCD4 in EM, we detected the expression of PDCD4 in control endometrium and eutopic/ectopic endometrium of ovarian EM patients, and analyzed the effects of PDCD4 on the biological behaviors of endometrial cell lines and primary endometrial cells. The results demonstrated that PDCD4 was downregulated in eutopic and ectopic endometrium of EM patients compared with control endometrium. PDCD4 effectively inhibited the proliferation and colony-forming ability of endometrial cells maybe by inhibiting cell autophagy. In addition, PDCD4 also suppressed the migration and invasion ability of endometrial cells, the mechanism may be related to NF-κB/MMP2/MMP9 signal pathway. Taken together, these results suggest that PDCD4 could be involved in the pathogenesis of EM, and provide a novel approach to target the aberrant PDCD4 expression in EM.

The decreased expression of TIPE2 protein in the decidua of patients with missed abortion and possible significance.

BACKGROUND: Missed abortion is a common occurrence for otherwise healthy women. Immunological factor is one of the most important reasons. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) is a novel negative immune regulator related to several human diseases. However, the expression level and clinical significance of TIPE2 in missed abortion remain unclear. METHODS: The expression of TIPE2 mRNA and protein in decidua and chorion from 36 missed abortion patients and 36 healthy controls was detected using quantitative real-time PCR, western blot and immunohistochemistry. In addition, serum TNF-ɑ and IL-10 levels were measured using flow cytometry. Serum estradiol and progesterone levels were measured by radioimmunoassay test. The correlations of TIPE2 protein levels with TNF-ɑ, IL-10, estradiol and progesterone were further analyzed. RESULTS: TIPE2 protein levels were significantly lower in decidual tissues of missed abortion patients than those in healthy controls. The patients with missed abortion had significantly higher levels of serum TNF-ɑ, and lower levels of serum IL-10, estradiol and progesterone compared with healthy controls. The TIPE2 protein levels were positively related to serum IL-10 levels. CONCLUSION: Our data indicate TIPE2 could play important roles in maintaining the maternal-fetal tolerance and decreased TIPE2 expression in the decidua may be related to the development of missed abortion.

Broadband Photodetector Based on FePS3/WS2 van der Waals Type II Heterostructure.

In order to understand broadband photodetectors from ultraviolet-visible (UV-vis) to the near-infrared range, one needs to find novel two-dimensional (2D) van der Waals (vdW) materials with broadband optoelectronic performance. Transition metal phosphorus sulfides (TMPSs) have been reported as a new type of vdW material with generally broadband and p-type conductivity. Here, we report a high-performance and broadband photodetector consist of p-type FePS3 and n-type WS2 with a working range of 405-785 nm. The maximum values of responsivity and specific detectivity are 32.5 mA/W and 1.73 × 1012 jones at 405 nm and 2 V bias, which are better than those of its individual constituents and many other 2D vdW heterostructures. The high performance of the FePS3/WS2 photodetector is attributed to the built-in electric field in the FePS3/WS2 p-n heterostructure and type II band alignment. Present study demonstrates that the material family of TMPSs could be a promising platform for broadband photodetector applications.

Apoptotic cell death induced by Z-Ligustilidein human ovarian cancer cells and role of NRF2.

Z-Ligustilide is the most potent bioactive component of Angelica sinensis, which is widely used in Chinese traditional medicine. Z-Ligustilide selectively affected ovarian cancer cell survival in a dose dependent manner. Z-Ligustilide induced apoptotic cell death was determined by flow cytometry. We also demonstrated that apoptotic cell death was triggered by Z-Ligustilideinduced oxidative stress and mitochondria played an active role. Mitochondrial polarization was reduced by Z-Ligustilidewhereas mitochondrial superoxide formation was increased. NRF2 was induced by Z-Ligustilide in OVCAR-3 cells at epigenetic level and its downstream antioxidant defense genesHeme oxygenase-1,NAD(P)H Quinone Dehydrogenase 1, UDP Glucuronosyltransferase Family 1 Member A1and Glutamate-Cysteine Ligase. NRF2 knockdown by siRNA resulted increased cell death by Z-Ligustilide in ovarian cancer cells. Our result demonstrated the pro-survival role of NRF2 in Z-Ligustilide induced ovarian cancer cell death.

The Expression of PDCD4 in Patients With Missed Abortion and Its Clinical Significance.

Missed abortion is a special form of spontaneous abortion and its incidence shows a rising trend. Immunological factor is one of the most common reasons. Tumor suppressor gene programmed cell death 4 ( PDCD4) also participates in some immune-mediated inflammation, such as atherosclerosis, and so on, but the role of PDCD4 in missed abortion remains unclear. Here, the expression of PDCD4 was detected in decidual and chorionic tissues, as well as peripheral blood mononuclear cells from patients with missed abortion and healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. The expression of cytokines was also detected in decidual tissues using qRT-PCR. The levels of serum estradiol and progesterone were measured by radioimmunoassay. In addition, the correlations of PDCD4 expression with cytokines and hormones were analyzed. The results demonstrated that PDCD4 expression was reduced in decidual tissues from the missed abortion group compared with the control group. The levels of tumor necrosis factor α were significantly higher in decidual tissues of missed abortion patients than those in normal controls. We also found serum estradiol and progesterone levels were significantly lower in the missed abortion group than those in the control group, and serum progesterone level was inversely related to PDCD4 messenger RNA level. The data suggested that reduced PDCD4 expression may be involved in the occurrence of missed abortion. This may facilitate the potential development of novel diagnostic and therapeutic strategies for the treatment of missed abortion.

A highly selective potentiometric sensor of molybdate based on a mu-oxo-bridged manganeseporphyrin dimer.

A novel high-selective potentiometric sensor for molybdate was prepared with a PVC membrane combining mu-oxo-bis[5,10,15,20-tetra(p-methylphenyl)porphinatomanganese(III)] [[Mn(p-Me)TPP](2)O] as an electroactive material and 2-nitrophenyl octyl ether (o-NPOE) as a plasticizer in the percentage ratio of 3:65:32, [Mn(p-Me)TPP](2)O:o-NPOE:PVC (w:w). The sensor exhibited a linear response with a Nernstian slope of 30.5 mV per decade within a concentration range of 2.1 x 10(-6) to 1.0 x 10(-1) M MoO4(2-), with a working pH range from 5.0 to 12.5, and a fast response time of less than 15 s. The electrode showed improved selectivity toward molybdate with respect to common coexisting anions compared to monometalloporphyrin counterparts. Several electroactive materials and solvent mediators were compared and the experimental conditions were optimized. The sensor is preliminary applied to the assay of MoO4(2-) in corrosion inhibitor samples with satisfactory results.

Epac1 knockdown inhibits the proliferation of ovarian cancer cells by inactivating AKT/Cyclin D1/CDK4 pathway in vitro and in vivo.

Ovarian cancer is the leading cause of death among gynecological malignancies, and high grade serous ovarian carcinoma is the most common and most aggressive subtype. Recently, it was demonstrated that cAMP mediates protein kinase A-independent effects through Epac (exchange protein directly activated by cAMP) proteins. Epac proteins, including Epac1 and Epac2, are implicated in several diverse cellular responses, such as insulin secretion, exocytosis, cellular calcium handling and formation of cell-cell junctions. Several reports document that Epac1 could play vital roles in promoting proliferation, invasion and migration of some cancer cells. However, the expression levels and roles of Epac1 in ovarian cancer have not been investigated. In the present study, we detected the expression levels of Epac1 mRNA and protein in three kinds of ovarian cancer cells SKOV3, OVCAR3 and CAOV3. Furthermore, the effect of Epac1 knockdown on the proliferation and apoptosis of SKOV3 and OVCAR3 cells was evaluated in vitro and in vivo. The results showed that there was higher expression of Epac1 mRNA and protein in SKOV3 and OVCAR3 cells. Epac1 knockdown inhibited the proliferation of SKOV3 and OVCAR3 cells in vitro and in vivo. Decreased proliferation may be due to downregulation of Epac1-induced G1 phase arrest by inactivating the AKT/Cyclin D1/CDK4 pathway, but not to alterations in the MAPK pathway or to apoptosis. Taken together, our data provide new insight into the essential role of Epac1 in regulating growth of ovarian cancer cells and suggest that Epac1 might represent an attractive therapeutic target for treatment of ovarian cancer.

Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells.

Resveratrol (trans-3,4,5'-trihydroxystilbene) is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3) was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS) generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.

A preliminary study on the construction of double suicide gene delivery vectors by mesenchymal stem cells and the in vitro inhibitory effects on SKOV3 cells.

The aim of the present study was to investigate the efficacy of using human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) as gene delivery vectors in the treatment of ovarian cancer. Lentivectors overexpressing cytosine deaminase (CD) and herpes simplex virus thymidine kinase (HSV-tk) (pGC-FU-CD-TK) were constructed, and confirmed by enzyme digestion, DNA sequence and western blotting. Quantitative PCR (PCR) was used to verify the overexpression of the fusion gene (CD and HSV-tk). SKOV3 cells were co-cultured with MSCs/tk+CD+ at a 1:1 ratio, and were then treated with the prodrugs (GCV) and/or 5-fluorocytosine (5-FC) at different concentrations, and the cytotoxic effects were evaluated using MTT assay and flow cytometry. DNA sequencing demonstrated that the sequence of HSV-tk and CD genes were consistent with the objective sequence and western blotting verified that the constructed lentivector could produce the HSV-tk/CD gene. The packed titer was 2.00e+8 TU/ml. The pGC-FU-CD-TK could be stably transferred to hUCB­MSCs, and the infection efficiency was almost 80%. RT-PCR demonstrated that the expression levels of the HSV-tk/CD fusion gene in MSCs/tk+CD+ group was 75 times that in the negative control (P<0.05). Compared with GCV or 5-FC alone, the growth inhibition rate (GIR) was significantly higher in the combined treatment (F=85.35, P<0.05). The reconstructed MSCs/tk+CD+ vectors were capable of slowing down the growth of human SKOV3 cells in the presence of prodrugs in vitro. The use of combination chemotherapy exhibited a more significant inhibitory effect than using a single prodrug.

Somatostatin derivative (smsDX) targets cellular metabolism in prostate cancer cells after androgen deprivation therapy.

Cancer cell metabolism responsive to androgen deprivation therapy (ADT) may be involved in the development and progression of prostate cancer and the ultimate failure of androgen-deprivation therapy. To investigate the metabolism regulation effects on androgen-independent growth of prostate cancer, an established LNCaP-s cell model that resembles the clinical scenario of castration-resistant prostate cancer (CRPC), was used in this current study. This cell line was cultured from androgen-sensitive LNCaP parental cells, in an androgen-reduced condition, resembling clinical androgen deprivation therapy. To assess the effects of smsDX on the invasiveness of prostate cancer cells we used wound healing assay and Matrigel™ invasion assay. We evaluated differentially expressed proteins of the parental LNCaP cells and LNCaP-s cells after ADT by means of two-dimensional gel electrophoresis (2-DE) followed by MALDI-TOF mass spectrometric analysis. The covered area in the wound and the number of cells invading through a Matrigel chamber were significantly smaller for cells treated with smsDX than they were for control cells treated with vehicle. 56 proteins were found differentially expressed in LNCaP-s cells compared to LNCaP cells, majority of them were down-regulated after ADT treatment. 104 proteins of LNCaP cells and 86 in LNCaP-s cells, separately, were found differentially expressed after treatment with smsDX, When we explored these protein functions within the website UniProtKB/Swiss-Prot, surprisingly, most of the proteins were found to be involved in the cellular metabolism and mitochondrial function regulation. LNCaP-s as potential metastatic androgen-independent cancer cells, its metabolism and mitochondrial functions could be altered by a new somatostatin derivative smsDX, the smsDX regulatory effects on metabolism in LNCaP-s deliver more therapeutic information with the treatment of CRPC.