scholarly journals Suppression of Ovarian Cancer Cell Growth by AT-MSC Microvesicles

2020 ◽  
Vol 21 (23) ◽  
pp. 9143
Author(s):  
Agnieszka Szyposzynska ◽  
Aleksandra Bielawska-Pohl ◽  
Agnieszka Krawczenko ◽  
Olga Doszyn ◽  
Maria Paprocka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Metabolic Activity ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Target Cells ◽  
Effective Transfer

Transport of bioactive cargo of microvesicles (MVs) into target cells can affect their fate and behavior and change their microenvironment. We assessed the effect of MVs derived from human immortalized mesenchymal stem cells of adipose tissue-origin (HATMSC2-MVs) on the biological activity of the ovarian cancer cell lines ES-2 (clear cell carcinoma) and OAW-42 (cystadenocarcinoma). The HATMSC2-MVs were characterized using dynamic light scattering (DLS), transmission electron microscopy, and flow cytometry. The anti-tumor properties of HATMSC2-MVs were assessed using MTT for metabolic activity and flow cytometry for cell survival, cell cycle progression, and phenotype. The secretion profile of ovarian cancer cells was evaluated with a protein antibody array. Both cell lines internalized HATMSC2-MVs, which was associated with a decreased metabolic activity of cancer cells. HATMSC2-MVs exerted a pro-apoptotic and/or necrotic effect on ES-2 and OAW-42 cells and increased the expression of anti-tumor factors in both cell lines compared to control. In conclusion, we confirmed an effective transfer of HATMSC2-MVs into ovarian cancer cells that resulted in the inhibition of cell proliferation via different pathways, apoptosis and/or necrosis, which, with high likelihood, is related to the presence of different anti-tumor factors secreted by the ES-2 and OAW-42 cells.

LncRNA SDHAP1 confers paclitaxel resistance of ovarian cancer by regulating EIF4G2 expression via miR-4465

2020 ◽  
Vol 168 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Hui Zhao ◽  
Aixia Wang ◽  
Zhiwei Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Regulatory Function ◽  
Ovarian Cancer Cells ◽  
Chemotherapeutic Resistance ◽  
Ovarian Cancer Cell Lines

Abstract Ovarian cancer has ranked as one of the leading causes of female morbidity and mortality around the world, which affects ∼239,000 patients and causes 152,000 deaths every year. Chemotherapeutic resistance of ovarian cancer remains a devastating actuality in clinic. The aberrant upregulation of long non-coding RNA succinate dehydrogenase complex flavoprotein subunit A pseudogene 1 (lncRNA SDHAP1) in the Paclitaxel (PTX)-resistant ovarian cancer cell lines has been reported. However, studies focussed on SDHAP1 in its regulatory function of chemotherapeutic resistance in ovarian cancer are limited, and the detailed mechanisms remain unclear. In this study, we demonstrated that SDHAP1 was upregulated in PTX-resistant SKOV3 and Hey-8 ovarian cancer cell lines while the level of miR-4465 was downregulated. Knocking-down SDHAP1 induced re-acquirement of chemo-sensitivity to PTX in ovarian cancer cells in vitro. Mechanically, SDHAP1 upregulated the expression of EIF4G2 by sponging miR-4465 and thus facilitated the PTX-induced apoptosis in ovarian cancer cells. The regulation network involving SDHAP1, miR-4465 and EIF4G2 could be a potential therapy target for the PTX-resistant ovarian cancer.

scholarly journals LHRH might act as a negative autocrine regulator of proliferation of human ovarian cancer

2000 ◽  
pp. 665-670 ◽  
Author(s):  
G Emons ◽  
S Weiss ◽  
O Ortmann ◽  
C Grundker ◽  
KD Schulz
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Lhrh Agonists ◽  
Ovarian Cancer Cell Lines ◽  
Low Concentrations

OBJECTIVE: More than 80% of human ovarian cancers express LHRH and its receptor. The proliferation of human ovarian cancer cell lines is reduced by both LHRH agonists and antagonists. This study was designed to further clarify the possible biological function of this LHRH system. DESIGN: As LHRH agonists and antagonists uniformly reduce proliferation of human ovarian cancer in a dose-dependent way, the effect of low concentrations of authentic LHRH was studied. In addition, longer periods of treatment (up to 9 days) were analyzed. To assess the physiological role of LHRH produced by ovarian cancer cells it was neutralized by adequate concentrations of a specific LHRH antiserum. METHODS: Human ovarian cancer cells EFO-21 and EFO-27, which express LHRH and its receptor, were incubated for 1-9 days with increasing concentrations (1pmol/l to 10 micromol/l) of authentic LHRH or with concentrations of LHRH antiserum capable of neutralizing at least 1nmol/l LHRH. Proliferation was assessed by counting cells. RESULTS AND CONCLUSIONS: Authentic LHRH reduced time- and dose-dependently proliferation (by maximally mean+/-s.e.m. 32.7 +/- 4.4%, Newman-Keuls, P < 0.001) of both ovarian cancer cell lines. At very low concentrations (1pmol/l) a marginal reduction of proliferation or no effect was observed. A mitogenic effect of authentic LHRH was never detected. Treatment of ovarian cancer cell cultures with antiserum to LHRH significantly increased (up to mean+/-s.e.m. 121.0 +/- 2.8% of controls, Newman-Keuls P <0.001) proliferation of EFO-21 and EFO-27 cells. These findings suggest that LHRH produced by human ovarian cancer cells might act as a negative autocrine regulator of proliferation.

ID: 45: EVALUATION OF CELLULAR MECHANISMS BY WHICH CINOBUFOTALIN INHIBITS OVARIAN CANCER CELL LINES FUNCTION

2016 ◽  
Vol 64 (4) ◽  
pp. 950.1-950 ◽  
Author(s):  
SH Afroze ◽  
DC Zawieja ◽  
R Tobin ◽  
C Peddaboina ◽  
MK Newell-Rogers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Ovarian Cancer Cell Lines

ObjectiveCinobufotalin (CINO), a cardiotonic steroid (CTS) or bufadienolide, is extracted from the skin secretions of the traditional Chinese medicine giant toads (Chan su). CINO has been used as a cardiotonic, diuretic and a hemostatic agent. Previously we have shown that CINO inhibits the cytotrophoblast cell function. Recently other study has shown that CINO inhibits A549, a lung cancer cell function. In this study, we assessed the effect of CINO on three different ovarian cancer cell lines; SK-OV-3, CRL-1978 and CRL-11731 to confirm whether the effect of CINO is cell specific.Study DesignWe evaluated the effect of CINO on three ovarian cancer cells SK-OV-3, CRL-1978, and CRL-11731 function in vitro. Each Cell lines were treated with different concentrations of CINO (0.1, 1, 5 and 10 µM). For each cell line cell proliferation, migration and invasion were measured by using a CellTiter Assay (Promega), Cytoselect Assay (Cell Biolabs) and by using a FluoroBlock Assay (BD) respectively. Proliferating Cell Nuclear Antigen (PCNA) was also evaluated in cell lysates of CINO treated these 3 ovarian cancer cells by western blot analysis. Cell Cycle arrest and Cell viability were determined by fluorescence-activated cell sorting (FACS) analysis. We also performed Annexin V staining on CINO treated these 3 ovarian cancer cell lines by immunofluorescence to evaluate the pro-apoptotic protein expression. In addition mitochondrial membrane potential has also been measured for all these 3 ovarian cell lines after CINO treatment using MMP kit, by FACS analysis.ResultsConcentration of CINO at 0.5 µM inhibit SK-OV-3, CRL-1978, and CRL-11731 ovarian cancer cells proliferation, migration and invasion without cell death and loss of cell viability but cell viability differs for each cell line. Each cell lines differ in response to CINO doses for PCNA expression as well as Annexin V pro-apoptotic protein expression. CINO decreases mitochondrial membrane potential for SK-OV-3 but for CRL-1978 and CRL-11731 increases in response to CINO treatment.ConclusionCINO is cell specific, as each cancer cell line responds differently. These data demonstrate that the mode of action of CINO is different on these 3 types of ovarian cancer cells.

scholarly journals Regulator of G-protein signalling expression and function in ovarian cancer cell lines

2009 ◽  
Vol 14 (1) ◽  
Author(s):  
Jillian Hurst ◽  
Nisha Mendpara ◽  
Shelley Hooks
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
G Protein ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Rgs Proteins ◽  
Ovarian Cancer Cell Lines

AbstractRegulator of G-protein signalling (RGS)2 proteins critically regulate signalling cascades initiated by G-protein coupled receptors (GPCRs) by accelerating the deactivation of heterotrimeric G-proteins. Lysophosphatidic acid (LPA) is the predominant growth factor that drives the progression of ovarian cancer by activating specific GPCRs and G-proteins expressed in ovarian cancer cells. We have recently reported that RGS proteins endogenously expressed in SKOV-3 ovarian cancer cells dramatically attenuate LPA stimulated cell signalling. The goal of this study was twofold: first, to identify candidate RGS proteins expressed in SKOV-3 cells that may account for the reported negative regulation of G-protein signalling, and second, to determine if these RGS protein transcripts are differentially expressed among commonly utilized ovarian cancer cell lines and non-cancerous ovarian cell lines. Reverse transcriptase-PCR was performed to determine transcript expression of 22 major RGS subtypes in RNA isolated from SKOV-3, OVCAR-3 and Caov-3 ovarian cancer cell lines and non-cancerous immortalized ovarian surface epithelial (IOSE) cells. Fifteen RGS transcripts were detected in SKOV-3 cell lines. To compare the relative expression levels in these cell lines, quantitative real time RT-PCR was performed on select transcripts. RGS19/GAIP was expressed at similar levels in all four cell lines, while RGS2 transcript was detected at levels slightly lower in ovarian cancer cells as compared to IOSE cells. RGS4 and RGS6 transcripts were expressed at dramatically different levels in ovarian cancer cell lines as compared to IOSE cells. RGS4 transcript was detected in IOSE at levels several thousand fold higher than its expression level in ovarian cancer cells lines, while RGS6 transcript was expressed fivefold higher in SKOV-3 cells as compared to IOSE cells, and over a thousand fold higher in OVCAR-3 and Caov-3 cells as compared to IOSE cells. Functional studies of RGS 2, 6, and 19/GAIP were performed by measuring their effects on LPA stimulated production of inositol phosphates. In COS-7 cells expressing individual exogenous LPA receptors, RGS2 and RSG19/GAIP attenuated signalling initiated by LPA1, LPA2, or LPA3, while RGS6 only inhibited signalling initiated by LPA2 receptors. In SKOV-3 ovarian cancer cells, RGS2 but not RGS6 or RGS19/GAIP, inhibited LPA stimulated inositol phosphate production. In contrast, in CAOV-3 cells RGS19/GAIP strongly attenuated LPA signalling. Thus, multiple RGS proteins are expressed at significantly different levels in cells derived from cancerous and normal ovarian cells and at least two candidate RGS transcripts have been identified to account for the reported regulation of LPA signalling pathways in ovarian cancer cells.

LY294002 and Metformin Cooperatively Enhance the Inhibition of Growth and the Induction of Apoptosis of Ovarian Cancer Cells

2012 ◽  
Vol 22 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Cuilan Li ◽  
Vincent Wing Sun Liu ◽  
David Wai Chan ◽  
Kwok Ming Yao ◽  
Hextan Yuen Sheung Ngan
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Flow Cytometry ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Mtor Pathway ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Growth

BackgroundThe phosphoinositide 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (AKT)/mammalian target of rapamycin (mTOR) pathway is frequently aberrantly activated in ovarian cancer and confers the chemoresistant phenotype of ovarian cancer cells. LY294002 (PI3K inhibitor) and metformin (5′-adenosine monophosphate [AMP]-activated protein kinase [AMPK] activator) are 2 drugs that were known to inhibit mTOR expression through the AKT-dependent and AKT-independent pathways, respectively. In this study, we explored the effectiveness of LY294002 and metformin in combination on inhibition of ovarian cancer cell growth.MethodsWestern blotting was used to detect the changes of PI3K/AKT/mTOR and AMPK/acetyl-CoA carboxylase (ACC) signaling activities, cell cycle control, and apoptosis. Cell growth was evaluated by cell proliferation, colony formation, and soft agar assays. Flow cytometry was used to study cell cycle distribution and cell death upon drug treatment.ResultsOur study showed that LY294002 and metformin in combination could simultaneously enhance the repression of the PI3K/AKT/mTOR pathway and the activation of the AMPK/ACC pathway. The downstream target of AKT and AMPK, mTOR, was cooperatively repressed when the drugs were used together. The cell cycle regulatory factors, p53, p27, and p21, were up-regulated. On the other hand, caspase 3 and poly (ADP-ribose) polymerase activities involved in apoptosis were also activated. Cell growth assays indicated that LY294002 and metformin could effectively inhibit ovarian cancer cell growth. Flow cytometry analysis showed that the treatment of the 2 drugs mentioned above induced cell cycle arrest at G1 phase and increased sub-G1 apoptotic cells.ConclusionThe combinational use of LY294002 and metformin can enhance inhibition of the growth and induction of the apoptosis of ovarian cancer cells. Our results may provide significant insight into the future therapeutic regimens in ovarian cancer.

scholarly journals Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through the GnRH type I receptor

2004 ◽  
pp. 141-149 ◽  
Author(s):  
C Grundker ◽  
L Schlotawa ◽  
V Viereck ◽  
N Eicke ◽  
A Horst ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Antiproliferative Effects ◽  
Ovarian Cancer Cell Lines

BACKGROUND: The majority of human endometrial and ovarian cancer cell lines express receptors for GnRH. Their proliferation is time- and dose-dependently reduced by GnRH-I and its superagonistic analogues. Recently, we have demonstrated that, in human endometrial and ovarian cancer cell lines except for the ovarian cancer cell line EFO-27, the GnRH-I antagonist cetrorelix has antiproliferative effects comparable to those of GnRH-I agonists, indicating that the dichotomy between GnRH-I agonists and antagonists might not apply to the GnRH system in cancer cells. We were also able to show that the proliferation of human endometrial and ovarian cancer cells was dose- and time-dependently reduced by GnRH-II to a greater extent than by GnRH-I agonists. OBJECTIVE: In this study we have assessed whether or not the antiproliferative effects of the GnRH-I antagonist cetrorelix in endometrial and ovarian cancer cells are mediated through the GnRH-I receptor. METHODS: We analysed the antiproliferative effects of the GnRH-I agonist triptorelin, the GnRH-I antagonist cetrorelix and GnRH-II in a panel of endometrial and ovarian cancer cell lines expressing GnRH-I receptors, in the SK-OV-3 ovarian cancer cell line that does not express GnRH-I receptors, and in four GnRH-I receptor positive GnRH-I receptor knockout cell lines. RESULTS: We found that, after knockout of the GnRH-I receptor, the antiproliferative effects of the GnRH-I agonist triptorelin were abrogated, whereas those of the GnRH-I antagonist cetrorelix and of GnRH-II persisted. CONCLUSIONS: These data suggest that, in endometrial and ovarian cancer cells, the antiproliferative effects of cetrorelix and of GnRH-II are not mediated through the GnRH-I receptor.

scholarly journals Tripartite Motif Containing 37 Activates the Wnt/β-catenin Signalling Pathway and Confers Cisplatin Resistance to Ovarian Carcinoma

2020 ◽  
Author(s):  
Jin xin Liu ◽  
Dapeng Ding ◽  
FEIYE LIU ◽  
Yizhi Chen
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cisplatin Resistance ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Ovarian Cancer Cell Lines ◽  
Tripartite Motif

Abstract Background Emerging evidence shows that the deregulation of tripartite motif (TRIM) family proteins have various functions in cellular processes and play important role in innate immunity, nervous system diseases, protein quality control and carcinogenesis. However, the precise biological function and molecular mechanism of TRIM family proteins in ovarian cancer chemo-resistance remain unclear. Methods The protein and mRNA expression of TRIM37 in ovarian cancer cell lines and patient tissues were determined using Real-time PCR and Western blot and IHC respectively. Functional assays, such as MTT, FACS, and Tunel assay used to determine the oncogenic role of TRIM37 in human ovarian cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM37 promotes chemoresistance in ovarian cancer cells. Results Herein, we found that the protein and mRNA expression of TRIM37 were markedly overexpressed in ovarian cancer tissues which shown partially responded to cisplatin chemotherapy. Moreover, TRIM37 expression was inversely correlated with patient survival in our cohort HCC tissue samples and public HCC database. Overexpression of TRIM37 confers cisplatin resistance on ovarian cancer cells; but, inhibition of TRIM37 sensitized ovarian cancer cell lines to cisplatin cytotoxicity both in vitro and in vivo. Additionally, TRIM37 upregulated the levels of nuclear β-catenin, thereby activating canonical wnt/β-catenin signaling. Conclusions our results demonstrate that targeting TRIM37/β-catenin axis may represent a promising strategy to enhance cisplatin response in patients with chemo-resistant ovarian cancer.

scholarly journals Transcriptome Remodeling in Gradual Development of Inverse Resistance between Paclitaxel and Cisplatin in Ovarian Cancer Cells

2020 ◽  
Vol 21 (23) ◽  
pp. 9218
Author(s):  
Jolanta Szenajch ◽  
Alicja Szabelska-Beręsewicz ◽  
Aleksandra Świercz ◽  
Joanna Zyprych-Walczak ◽  
Idzi Siatkowski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Resistance Development ◽  
Receptor Family

Resistance to anti-cancer drugs is the main challenge in oncology. In pre-clinical studies, established cancer cell lines are primary tools in deciphering molecular mechanisms of this phenomenon. In this study, we proposed a new, transcriptome-focused approach, utilizing a model of isogenic cancer cell lines with gradually changing resistance. We analyzed trends in gene expression in the aim to find out a scaffold of resistance development process. The ovarian cancer cell line A2780 was treated with stepwise increased concentrations of paclitaxel (PTX) to generate a series of drug resistant sublines. To monitor transcriptome changes we submitted them to mRNA-sequencing, followed by the identification of differentially expressed genes (DEGs), principal component analysis (PCA), and hierarchical clustering. Functional interactions of proteins, encoded by DEGs, were analyzed by building protein-protein interaction (PPI) networks. We obtained human ovarian cancer cell lines with gradually developed resistance to PTX and collateral sensitivity to cisplatin (CDDP) (inverse resistance). In their transcriptomes, we identified two groups of DEGs: (1) With fluctuations in expression in the course of resistance acquiring; and (2) with a consistently changed expression at each stage of resistance development, constituting a scaffold of the process. In the scaffold PPI network, the cell cycle regulator—polo-like kinase 2 (PLK2); proteins belonging to the tumor necrosis factor (TNF) ligand and receptor family, as well as to the ephrin receptor family were found, and moreover, proteins linked to osteo- and chondrogenesis and the nervous system development. Our cellular model of drug resistance allowed for keeping track of trends in gene expression and studying this phenomenon as a process of evolution, reflected by global transcriptome remodeling. This approach enabled us to explore novel candidate genes and surmise that abrogation of the osteomimic phenotype in ovarian cancer cells might occur during the development of inverse resistance between PTX and CDDP.

scholarly journals Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines

Oncotarget ◽  
2016 ◽  
Vol 7 (29) ◽  
pp. 46120-46126 ◽  
Author(s):  
Kamila Kloudová ◽  
Hana Hromádková ◽  
Simona Partlová ◽  
Tomáš Brtnický ◽  
Lukáš Rob ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumor Antigens ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Primary Ovarian Cancer ◽  
Ovarian Cancer Cell Lines
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