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PURPOSE: Ovarian cancer is a devastating gynecological disease which is considered the major cause of cancer fatality around the world. The down-regulation of microRNA-33b (miR-33b) was reported in some malignancies. Hence, we transfected the miR-33b mimic into SKOV3 cells and evaluated the impacts of this interference on the growth and migration repression of these tumor cells as well as on targeted genes expression. METHODS: In our study, transfecting the miR-33b mimic and inhibitor, negative control (NC), and NC inhibitor were established using Lipofectamine 2000. The cytotoxic effects of miR-33b were evaluated by MTT. To assess the miR-33b effects on cell migration, a scratching test was applied. The expression levels of miR-33b, ADAMTS, C-Myc, MMP9, K-Ras, and CXCR4 were evaluated using qRT-PCR. RESULTS: These findings indicate that transfection of miR-143 mimic had no marked effects on the SKOV3 cell line. As expected, miR-33b relative expression levels were as follows: miR-33b mimic >NC and NC inhibitor >miR-33b inhibitor (p < 0.01). Moreover, transfected miR-33b mimic could suppress SKOV3 cells' proliferation, whereas transfected miR-33b inhibitor could promote cell proliferation (p < 0.01). MiR-33b overexpression significantly down-regulated the MMP9, CXCR-4, c-Myc, ADAMTS, and K-Ras mRNA levels (p < 0.05). CONCLUSION: As expected, these results confirm the tumor-suppressive effect of miR-33b in the SKOV3 ovarian cancer cell line by reducing cell survival, proliferation, and migration.
Assuntos
Antineoplásicos , MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Linhagem Celular Tumoral , Neoplasias Ovarianas/metabolismo , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão GênicaRESUMO
Cyclophosphamide (CP) is very well-known anticancer drug and commonly used against various cancers. CP therapy is related to female ovarian cancer and causes female infertility. The ovarian cancer associated with the increase oxidative stress and inflammatory reaction. Syringic acid (SA) is very well phyto-constituent and already proof antioxidant and anti-inflammatory effects on various diseases. We investigated the chemoprotective impact of SA on CP mediated ovarian damage, and the underlying mechanism. CP (75 mg/kg) was used to cause ovarian damage and rats were randomly divided into separate groups and received a different dose of SA for 14-day. Body weight, food and water intake were determined. Ovarian weight and tumor index was measured. Antioxidant parameters were determined in the serum and ovarian tissue. Pro-inflammatory cytokines, apoptosis parameters and inflammatory mediators were estimated in the serum. Hormonal parameters and Histomorphometry were estimated. Dose dependently treatment of SA significantly (p < 0.001) decreased the levels of biochemical parameter such as nitric oxide (NO), myeloperoxidase (MPO) and augmented the antioxidant parameters include catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced malondialdehyde (MDA) level in serum and ovarian tissue. SA treatment significantly (p < 0.001) suppressed the level of luteinizing hormones (LH), anti-mullerian hormone (AMH), estradiol (E2) and folliclestimulating hormone (FSH) as well as ovarian follicles. SA significantly (p < 0.001) down-regulated cytokines, inflammatory mediator and caspase-3 parameters. Taken altogether, we conclude that SA considerably reduced ovarian damage via reduced oxidative stress and inflammatory reaction.
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Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Fitogênicos , Quimioprevenção , Ciclofosfamida/efeitos adversos , Ácido Gálico/análogos & derivados , Mediadores da Inflamação/metabolismo , Neoplasias Ovarianas/etiologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Ácido Gálico/administração & dosagem , Ácido Gálico/farmacologia , Humanos , Neoplasias Ovarianas/metabolismo , Ratos Wistar , Transdução de Sinais/genéticaRESUMO
microRNA-152 (miR-152) is a tumor suppressor that is down-regulated in many cancers including endometrial cancer (EC). However, the underlying mechanism of action of miR-152 in EC is unclear. The aim of the present study was to evaluate the role of miR-152 on proliferation of human endometrial cancer cells. Herein, we found that miR-152 overexpression and CDC25B knockdown inhibited proliferative ability and induced G2/M phase arrest in KLE and HEC-1B cells. CDC25B was a target of miR-152. In addition, CDC25B overexpression rescued miR-152-induced proliferation inhibition and G2/M phase arrest in human endometrial cancer cells. The results indicated that miR-152 was a tumor suppressor in EC that inhibited proliferation of human endometrial cancer cells via inducing G2/M phase arrest by suppressing CDC25B expression.
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Pontos de Checagem do Ciclo Celular/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Fase G2/genética , MicroRNAs/metabolismo , Mitose/genética , Fosfatases cdc25/genética , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , MicroRNAs/genética , RNA Interferente Pequeno/metabolismo , Fosfatases cdc25/metabolismoRESUMO
The present study aimed to explore the expression of microRNA (miRNA or miR) in drug-resistant and drug-sensitive ovarian cancer cell lines, and to seek the potential therapeutic target of ovarian cancer drug-resistant mechanism in order to improve drug resistance by altering miRNA levels. The drug-resistant characteristics of SKOV3/DDP, SKOV3, COC1/DDP and COC1 cell lines were studied. The miRNAs that were differentially expressed between cisplatin-resistant cells and its parental cells in ovarian cancer were screened with a miRNA chip. The effect of miRNAs was detected, and their drug-resistant mechanism was investigated by transfection and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods. Among the expression screening of miRNAs, 41 mRNAs, including Homo sapiens (hsa)-miR-30a-5p and hsa-miR-34c-5p, were highly expressed in the drug-resistant cells, whereas 44 miRNAs, including hsa-miR-96-5p and hsa-miR-200c-3p, were lowly expressed. The expression levels of hsa-miR-30a-5p in two types of ovarian cancer chemotherapy-resistant cell lines were significantly higher than those in chemotherapy-sensitive cell lines, which was associated with ovarian cancer chemotherapy resistance. In conclusion, high expression of miRNA-30a-5p was able to promote cell growth and colony forming ability, and enhance cell migration and invasion. Thus, miRNA-30a-5p is expected to become a meaningful novel target for ovarian cancer resistant treatment.
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OBJECTIVE: To study the inhibition effect of miR-106a inhibitor on tumor growth of ovarian cancer xenografts mice. METHODS: BALB/c mice were selected as experimental animals, ovarian cancer SKOV-3 cells transfected with miR-106a inhibitor and its negative control were inoculated subcutaneously, intratumoral injection of miR-106a inhibitor and its negative control were continued after tumor formation, and they were enrolled as treatment group and model group, respectively. Tumor volume and weight as well as Ki-67 and programmed cell death 4 (PDCD4) expression were determined; miR-106a inhibitor and its negative control as well as miR-106a mimic and its negative control were transfected into SKOV-3 cells, and expression of PDCD4 in cells was determined. RESULTS: Tumor tissue volume and weight as well as mRNA expression and protein expression of Ki-67 in treatment group were significantly lower than those in the model group while mRNA expression and protein expression of PDCD4 were significantly higher than those in the model group; transfection of miR-106a mimic could decrease mRNA expression and protein expression of PDCD4 in SKOV-3 cells, and transfection of miR-106a inhibitor could increase mRNA expression and protein expression of PDCD4 in SKOV-3 cells. CONCLUSIONS: Transfection of miR-106a inhibitor can inhibit the growth of tumor in ovarian cancer xenografts mice through increasing the expression of PDCD4.
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BACKGROUND: The aim of this study was to investigate the feasibility and clinical value of transvaginal surgical treatment for cesarean scar pregnancy (CSP-II). MATERIAL AND METHODS: This study was a retrospective analysis of 25 CSP-II patients who received transvaginal surgical treatments. These patients were admitted in our hospital between January 2010 and June 2012. RESULTS: All surgical treatments were successful without overt complications. The average operation time was 61.5 minutes, the average intraoperative blood loss was 60.5 ml, the average hospital stay was 9.4 days and the average time that blood ß-human chorionic gonadotropin (ß-HCG) returned to normal range was 15 days. In all 25 patients, the cesarean scar mass located at the anterior wall of the lower uterine segment disappeared by B-ultrasound examination within 1 or 2 weeks after surgery. Postoperatively, the normal menstrual period started again with an average time of 28.9 days. No menstruation-related abnormalities, such as menstrual dripping or an abnormal amount of blood, were reported after surgery. CONCLUSIONS: Transvaginal surgery for CSP-II is a novel surgical approach. It has several advantages, including a thorough one-time treatment lesion clearance, short operation time, minimized trauma, minimal intraoperative blood loss, quick reduction of blood ß-HCG, and rapid menstruation recovery. It is a simple and feasible surgical approach of great clinical value and few treatment-related complications.
Assuntos
Cesárea/efeitos adversos , Cicatriz/cirurgia , Gravidez Ectópica/cirurgia , Adulto , Perda Sanguínea Cirúrgica , Gonadotropina Coriônica Humana Subunidade beta/sangue , Feminino , Seguimentos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Duração da Cirurgia , Admissão do Paciente , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: The purpose of this study is to identify a prospective association between CA125 and tumorigenic ovarian cancer cells, using the new method of orthotopic transplantation (1). METHOD: After making the surgical ovarian cancer specimen into cell suspension, we separated the tumorigenic cells from the nontumorigenic cancer cells based on cell surface marker (cancer antigen CA125 and lineage markers) expression. We developed a SCID mice model in which the CA125+/ lineage- and CA125-/ lineage- cells were injected into ovarian parenchyma by use of a microinjector. As a measure of effectiveness of tumor-forming, tumor weight, abdominal distension, ascites volume and activity, subcutaneous fat were determined or observed. Immunohistochemistry was done to determine tumor cell markers. RESULTS: We found that the cells of CA125+/ lineage- were able to form new tumors; whereas, an equal quantity of CA125-/lineage- cells failed to form any tumors. The new generated tumor contained additional CA125-/lineage- tumorigenic cells as well as the phenotypically diverse population of nontumorigenic cells. Quantities were judged to be significantly different P < 0.0001. CONCLUSION: CA125+/ lineage- cells, which may be ovarian cancer stem cells, were the source for tumor recurrence. The strategies designed to target this cell population may lead to more effective therapies.
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Biomarcadores Tumorais/análise , Antígeno Ca-125/biossíntese , Proteínas de Membrana/biossíntese , Neoplasias Epiteliais e Glandulares/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/patologia , Animais , Antígeno Ca-125/análise , Carcinoma Epitelial do Ovário , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Xenoenxertos , Humanos , Proteínas de Membrana/análise , Camundongos , Camundongos SCID , Microscopia ConfocalRESUMO
A new technique has successfully established the non-obese diabetic/severely combined immunodeficiency (NOD/SCID) mouse model of ovarian cancer. Under 4% chloral hydrate (0.1 mL/g dose) anesthesia, female mice were inoculated with tumor-cell suspension. The expression rate of OVCAR3 to CA125 was assessed using flow cytometry. The inoculated site was hand palpated and the signs and symptoms related to tumor growth were observed with the naked eye. The allophycocyanin (APC) indirectly labeled mouse-antihuman CA125 and fluorescein isothiocyanate (FITC)-labeled anti-mouse MHC Class I molecule (H-2K(d)/H-2D(d)) were observed using a confocal laser scanning microscope. The animal model of ovarian cancer constructed using this method can more directly reflect the characteristics of cancer cells. It provides reliable experimental results and presents a technical platform for the research of ovarian cancer stem cells.