G Protein–Coupled Receptor 30 Mediates the Anticancer Effects Induced by Eicosapentaenoic Acid in Ovarian Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#While numerous epidemiological studies have indicated that omega-3 polyunsaturated fatty acids have anticancer properties in various cancers, the effects and mechanisms of eicosapentaenoic acid (EPA) in ovarian cancer cell growth are poorly understood. @*Materials and Methods@#ES2 ovarian clear cell carcinoma cells and SKOV3 adenocarcinoma cells were treated with palmitic acid or EPA, followed by flow cytometry and cell counting to measure apoptosis and proliferation, respectively. A modified protein lipid overlay assay was used to further verify whether EPA was a ligand of G protein–coupled receptor 30 (GPR30) in ES2 cells. The levels of apoptosis-related genes, phosphorylated AKT, and phosphorylated ERK1/2 were detected to explore the underlying mechanism. Finally, inhibitory effect of EPA on tumor growth via GPR30 was determined in vitro and in vivo. @*Results@#EPA suppressed ES2 ovarian clear cell carcinoma cells growth via GPR30, a novel EPA receptor, by inducing apoptosis. As a ligand of GPR30, EPA activated the GPR30-cAMP– protein kinase A signaling pathway. When GPR30 was suppressed by siRNA or its inhibitor G15, the antiproliferative action of EPA was impaired. Furthermore, EPA inhibited tumor growth by blocking the activation of AKT and ERK. In the mouse xenograft model, EPA decreased tumor volume and weight through GPR30 by blocking tumor cell proliferation. @*Conclusion@#These results confirm that EPA is a tumor suppressor in human ovarian clear cell carcinoma cells and functions through a novel fatty acid receptor, GPR30, indicating a mechanistic linkage between omega-3 fatty acids and cancers.

Research Progress of MicroRNA in Early Detection of Ovarian Cancer / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>This review aimed to update the progress of microRNA (miRNA) in early detection of ovarian cancer. We discussed the current clinical diagnosis methods and biomarkers of ovarian cancer, especially the methods of miRNA in early detection of ovarian cancer.</p><p><b>DATA SOURCES</b>We collected all relevant studies about miRNA and ovarian cancer in PubMed and CNKI from 1995 to 2015.</p><p><b>STUDY SELECTION</b>We included all relevant studies concerning miRNA in early detection of ovarian cancer, and excluded the duplicated articles.</p><p><b>RESULTS</b>miRNAs play a key role in various biological processes of ovarian cancer, such as development, proliferation, differentiation, apoptosis and metastasis, and these phenomena appear in the early-stage. Therefore, miRNA can be used as a new biomarker for early diagnosis of ovarian cancer, intervention on miRNA expression of known target genes, and potential target genes can achieve the effect of early prevention. With the development of nanoscience and technology, analysis methods of miRNA are also quickly developed, which may provide better characterization of early detection of ovarian cancer.</p><p><b>CONCLUSIONS</b>In the near future, miRNA therapy could be a powerful tool for ovarian cancer prevention and treatment, and combining with the new analysis technology and new nanomaterials, point-of-care tests for miRNA with high throughput, high sensitivity, and strong specificity are developed to achieve the application of diagnostic kits in screening of early ovarian cancer.</p>

Therapeutic effect of ovarian intra-arterial infusion of GE7-delivery system-mediated HSVl-tk/ganciclovir gene therapy in a rat model of malignant ovarian tumor / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the gene expression of herpes simplex virus type 1 thymidine kinase (HSVl-tk) in rat malignant ovarian tumor tissues and the therapeutic effect of ganciclovior (GCV) after intra-arterial infusion of HSVl-tk gene therapy mediated by GE7-delivery system.</p><p><b>METHODS</b>A GE7-polylysine/pCMV-HSV1-tk/polylysine-HA20 4-element complex was constructed. Eighteen rats with DMBA-induced ovarian tumor were divided into 3 groups as Atk, ANS and Vtk groups. The 4-element complex GE7-polylysine/pCMV-HSV1-tk/polylysine-HA20 was injected via the ovarian artery into the rats of Atk group, saline buffer was injected in the ANS groups, and the 4-element complex was injected via the tail vein into the rats of Vtk group. All rats received intraperitoneal injection of GCV in a dose of 50 mg/kg daily for 10 days. The rats were sacrificed 3 days after the final dose of GCV, and the tumor weight was measured and tumor growth inhibition rate was calculated. Flow cytometry was used to assess the cell cycle and apoptosis.</p><p><b>RESULTS</b>The tumor weight in the rats of Atk group was (4.77 ± 2.31) g, significantly lower than that of ANS group [(14.66 ± 6.26) g, P < 0.01] and Vtk group [(17.53 ± 7.19) g, P < 0.01]. The tumor growth inhibition rate of the Atk group was 67.5%, while that of Vtk group was -19.6%. The flow cytometry showed that S-phase tumor cells in the Atk group were (54.32 ± 9.65)%, significantly higher than that in the ANS (27.43 ± 9.22)% and (30.16 ± 11.57)% in the Vtk group (both P < 0.01). The tumor cell apoptosis rate in the Atk group was (39.15 ± 12.16)%, significantly higher than that in the ANS group [(11.86 ± 5.28)%, P < 0.01] and Vtk group [(14.32 ± 6.43)%, P < 0.01].</p><p><b>CONCLUSION</b>HSV1-tk/GCV gene therapy system mediated by GE7 non-viral delivery system via ovarian arterial infusion effectively causes cell cycle arrest at S phase and enhances cell apoptosis, therefore, exerts an inhibitory effect on tumor growth.</p>

Evaluation of GE7-transferring system-mediated HSV(1)-tk gene transfer in a rat model of ovarian tumor via intra-arterial route / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the gene and protein expression of herpes simplex virus type I-thymidine kinase (HSV(1)-tk) in the ovarian tumor tissues and other organs after arterial infusion of HSV(1)-tk gene mediated by GE7 delivery system.</p><p><b>METHODS</b>GE7-polylysine/pCMV-HSV(1)-tk/polylysine-HA20 complexes were constructed. Nine rats with induced ovarian tumor were divided into 3 groups, injecting the 4-element complexes or saline buffer through the ovarian artery and complexes through the tail vein, respectively. The ovarian tumors, hearts, livers, spleens, lungs and kidneys were obtained at 72 hours after injection. RT-PCR and Western Blot were preceeded to determine the expression of HSV(1)-tk gene and protein in the tumor tissues and other organs.</p><p><b>RESULTS</b>In the group of arterial injection with 4-element complexes, the HSV(1)-tk gene and protein were expressed strongly in the tumor tissues, while little or none was detected in other organs. In the group of arterial injection with saline buffer, no HSV(1)-tk gene and protein was detected in both tumor tissues and other organs. In the group of tail vein injection, none was detected in tumor tissues and only little was found in the livers, spleens, lungs and kidneys.</p><p><b>CONCLUSION</b>High target and gene transfer rates can be obtained when HSV(1)-tk gene is transferred via the artery route mediated by GE7 delivery system. HSV(1)-tk protein can be expressed after the gene transfer. The results may provide a new strategy for target killing of HSV(1)-tk/GCV system in ovarian tumors.</p>

Suicidal cancer vaccine enhances anti-tumor immunotherapeutic effect and its safety in the treatment of ovarian cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the anti-tumor immunotherapeutic effect induced by the suicidalcancer vaccine FC/TK, and to evaluate the safety of this vaccine.</p><p><b>METHODS</b>The suicidal cancer vaccine, named FC/TK, was prepared by fusion of suicide gene (HSVI,-TK gene) -modified ovarian carcinoma NuTu-19 cells with rat bone marrow-derived dendritic cells (DCs). The morphology of FC/TK was evaluated by scanning electron microscopy. The stimulatory effect of FC/TK on T cells was determined by T cell proliferation assay. In immunotherapeutic studies in vivo, Fischer344 rats were injected subcutaneously with NuTu-19 cells, followed by treatment of FC/TK on days 7 and 14, compared to controls treated with irradiated FC/TK, FC or PBS, respectively. Tumor incidence and volume were measured in 90 days after challenge. To determine the killing effect of FC/TK in vivo, TUNEL assays were applied to detect apoptotic cell death in spleen of vaccinated rats with prodrug ganciclovir administration.</p><p><b>RESULTS</b>FC/TK cells were of irregular shape with surface membrane processes. Compared to the control groups, FC/TK significantly promoted T cell proliferation (P <0.01). The rats vaccinated with FC/TK and FC significantly inhibited the tumor growth compared to rats vaccinated with irradiated FC/TK (P <0.05) or with PBS ( P <0.01). The immunotherapeutic effect induced by FC/TK was similar to that using FC. Fluorescence microscopy showed that fluorescein-stained FC/TK cells migrated into spleen also showed to be TUNEL-positive, suggesting that the FC/TK cells were killed by ganciclovir in vivo.</p><p><b>CONCLUSION</b>Our data indicate that suicidal cancer vaccine is an effective and safe therapy for ovarian carcinoma and may serve as a broadly applicable approach for other cancer vaccines in the future.</p>

Progress on the study of mechanism of the direct action of TCM bioactive components on ovarian cancer / 中国中西医结合杂志

Both the morbidity and mortality of ovarian cancer, among malignant tumors ot temale genital organs, are quite high. The traditional therapeutic methods on ovarian cancer are surgical operation, chemotherapy, radiotherapy and combination of these methods mentioned above. In recent years, some components of traditional Chinese medicine, such as genistein, semen Coicis, phytosterols, curcumin, quercetin, ginsenoside, etc. have been found to exert anticancer actions of inhibiting proliferation and inducing apoptosis of cancer cells, increasing the sensitivity of patients to chemotherapeutic agents in viva and/or in vitro, the mechanisms involve such aspects as inhibiting activity of key enzymes in cell metabolism, affecting gene expression, antioxidation, and inhibiting tumor angiogenesis, etc. As an adjuvant therapeutic means, the bioactive components of traditional Chinese medicine have broad future of clinical application.

Effect of bushen yiqi recipe on bioactivity behavior of human cytotrophoblast of early pregnancy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Chinese drugs for tonifying Shen on the bioactivity, cell proliferation, invasion and differentiation of human cytotrophoblast of early pregnancy.</p><p><b>METHODS</b>The human early pregnant cytotrophoblast was cultured in vitro, and treated with saline (as blank control) and drug containing serum in different concentrations (5%, 10% and 20%) respectively. The changes of morphology, proliferation and invasive capacity of cells were examined by scanning electron microscopy, MTT method, flow cytometry, Transwell invasive assay at 24 hrs, 48 hrs and 72 hrs after treatment.</p><p><b>RESULTS</b>After cells being cultured with drug containing serum, the cytotrophoblast became abundant in microvilli, with more and prolonged pseudopodia. The cell absorbency in 490 nm wave length increased significantly (P < 0.01), cells of sub-G1 and G2/M phase obviously decreased and that of S phase increased (P < 0.01), and the cells penetrated through PET membrane in each visual field significantly increased (P < 0.01).</p><p><b>CONCLUSION</b>Chinese herbs for tonifying Shen could promote the proliferation and invasive capacity of cytotrophoblast and might influence its differentiation.</p>

Impact of uterine fibroid embolization with danazol alginate microsphere on ovarian function and subsequent pregnancy / 中华妇产科杂志

0.05).Conclusions There is no obvious effect of danazol alginate microspheres used for uterine arterial embolization on ovarian function in rabblits.After UAE some animals are able to achieve pregnancies,while harmful effects are observed on short term pregnant rate.