scholarly journals Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells

2017 ◽  
Vol 43 (5) ◽  
pp. 1893-1906 ◽  
Author(s):  
Qiu-Xia Qu ◽  
Fang Xie ◽  
Qin Huang ◽  
Xue-Guang Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Immune Evasion ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Pi3k Pathway ◽  
Ovarian Cancer Cells ◽  
Tumor Growth Inhibition ◽  
Skov3 Cells

Background: Expression of programmed death-ligand 1 (PD-L1) on tumor cells represents a powerful immune evasion pathway, but the role of intracellular or cytoplasmic PD-L1 has not been investigated in ovarian cancer cells. Methods: Flow cytometry (FCM), Real-time PCR (qPCR), immunohistochemistry (IHC) and western blot were used to determine the expression of PD-L1 in ovarian cancer cells. The cytokines detected in the tumor or tumor associated macrophage (TAM) were used to treat cancer cells. PD-L1 blockade and silencing were used to elucidate the functional significance of cancer-related PD-L1 expression. Results: Based on the results presented, PD-L1 was found variably expressed in the cytoplasm and the cell surface of both HO8910 and SKOV3 cells. TAM or IFN-γ, TNF-α, IL-10 and IL-6 released from TAM stimulated the expression of PD-L1 at the surface of the cancer cells. The IHC results were consistent with the data in vitro showing infiltration of TAM correlated with membranous PD-L1. The increases of PD-L1 at the surface were not due to a shift in the proportion of surface versus intracellular protein, but the contribution of extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K) pathway activation. As a consequence, inducible membranous PD-L1 expression on SKOV3 inhibited CD8+ T cell function, and cytoplasmic PD-L1 promoted cancer cell growth. Additionally, in mouse models, both PD-L1 and PD-1 mAb resulted in tumor growth inhibition and demonstrated a potential to decrease the number of PD-1+CD8+T cells. Conclusion: We conclude that TAM induced PD-L1 on the cancer cells represents an immune evasion mechanism. The observations confirm the therapeutic potential of PD-L1/PD-1 mAb to reactivate anti-tumor immunity in ovarian cancer.

scholarly journals Effect of Ginsenoside Rh-2 via Activation of Caspase-3 and Bcl-2-Insensitive Pathway in Ovarian Cancer Cells

2016 ◽  
pp. 1031-1037 ◽  
Author(s):  
J. H. KIM ◽  
J.-S. CHOI
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Therapeutic Potential ◽  
Future Application ◽  
Ovarian Cancer Cells ◽  
Therapeutic Effects ◽  
Apoptosis Pathway ◽  
Skov3 Cells

Ginsenoside has been reported to have therapeutic effects for some types of cancer, but its effect on ovarian cancer cells has not been evaluated. In this study, we monitored the effects of ginsenoside-Rh2 (Rh2) on the inhibition of cell proliferation and the apoptotic process in the ovarian cancer cell line SKOV3 using an MTT assay and TUNEL assay. We found that Rh2 inhibited cell proliferation and significantly induced apoptosis. We confirmed the apoptotic effects of Rh2 using western blot analysis of apoptosis-related proteins. Specifically, the levels of cleaved poly ADP ribose polymerase (PARP) and cleaved caspase-3 significantly increased in SKOV3 cells treated with Rh2. Therefore, Rh2 clearly suppressed the growth of SKOV3 cells in vitro, which was associated with induction of the apoptosis pathway. Moreover, the migration assay showed that Rh2 inhibited the invasive ability of SKOV3 cells. Taken together, our results suggest that Rh2 has anticancer effects in SKOV3 cells through inhibition of cell proliferation and induction of apoptosis. Considering the therapeutic potential of Rh2, more studies should be carried out to facilitate the future application of this natural product as a potential anti-cancer agent.

scholarly journals DDP-resistant ovarian cancer cells-derived exosomal microRNA-30a-5p reduces the resistance of ovarian cancer cells to DDP

Open Biology ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 190173 ◽  
Author(s):  
Ronghua Liu ◽  
Yucan Zhang ◽  
Peiwen Sun ◽  
Changxiu Wang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Important Conclusion ◽  
Skov3 Cells ◽  
Potential Strategy

Exosomes carrying microRNAs (miRNAs) have been demonstrated to play critical roles in the regulation of development, growth and metastasis of cancer. Bioinformatic predictions identified differentially expressed SRY-box 9 (SOX9) in OC, and the regulatory miRNA miR-139-5p. Here, we aim to evaluate the function of exosomal miR-139-5p in the sensitivity of ovarian cancer (OC) cells to cis-diamminedichloroplatinum(II) (DDP). Expression pattern of miR-139-5p and SOX9 in ovarian cancer cells (SKOV3) and DDP-resistant cells (SKOV3/DDP) was identified using reverse transcription quantitative polymerase chain reaction and western blot analysis. The relationship between miR-139-5p and SOX9 was validated using a dual-luciferase reporter assay. SKOV3/DDP cell line was developed and introduced with miR-30a-5p mimic to analyse the effects of miR-30a-5p on resistance to DDP. The in vitro and in vivo effects of exosomal miR-30a-5p on resistance of SKOV3 cells to DDP were assessed in a co-culture system of exosomes and OC cells as well as in tumour-bearing nude mice. High expression of SOX9 and low expression of miR-30-5p were witnessed in OC. Furthermore, miR-30-5p, a downregulated miRNA in SKOV3/DDP cells, increased the rate of cell apoptosis and enhanced the sensitivity of SKOV3/DDP cells to DDP by targeting SOX9. Moreover, exosomes carrying miR-30a-5p were identified to sensitize SKOV3/DDP cells to DDP both in vitro and in vivo . These data together supported an important conclusion that DDP-resistant OC cell-derived exosomal miR-30a-5p enhanced cellular sensitivity to DDP, highlighting a potential strategy to overcome drug resistance.

Cytotoxic effects of disulfiram and synergism with cisplatin on ovarian cancer cells in vitro

2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cytotoxic Effects

scholarly journals Electrochemotherapy with Calcium Chloride and 17β-Estradiol Modulated Viability and Apoptosis Pathway in Human Ovarian Cancer

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 19
Author(s):  
Zofia Łapińska ◽  
Michał Dębiński ◽  
Anna Szewczyk ◽  
Anna Choromańska ◽  
Julita Kulbacka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Calcium Chloride ◽  
Morphological Changes ◽  
Cell Membrane Permeability ◽  
Immunocytochemical Staining ◽  
Ovarian Cancer Cells ◽  
Apoptosis Pathway ◽  
17Β Estradiol

Estrogens (Es) play a significant role in the carcinogenesis and progression of ovarian malignancies. Depending on the concentration, Es may have a protective or toxic effect on cells. Moreover, they can directly or indirectly affect the activity of membrane ion channels. In the presented study, we investigated in vitro the effectiveness of the ovarian cancer cells (MDAH-2774) pre-incubation with 17β-estradiol (E2; 10 µM) in the conventional chemotherapy (CT) and electrochemotherapy (ECT) with cisplatin or calcium chloride. We used three different protocols of electroporation including microseconds (µsEP) and nanoseconds (nsEP) range. The cytotoxic effect of the applied treatment was examined by the MTT assay. We used fluorescent staining and holotomographic imaging to observe morphological changes. The immunocytochemical staining evaluated the expression of the caspase-12. The electroporation process’s effectiveness was analyzed by a flow cytometer using the Yo-Pro™-1 dye absorption assay. We found that pre-incubation of ovarian cancer cells with 17β-estradiol may effectively enhance the chemo- and electrochemotherapy with cisplatin and calcium chloride. At the same time, estradiol reduced the effectiveness of electroporation, which may indicate that the mechanism of increasing the effectiveness of ECT by E2 is not related to the change of cell membrane permeability.

scholarly journals Genetic Perturbation of Pyruvate Dehydrogenase Kinase 1 Modulates Growth, Angiogenesis and Metabolic Pathways in Ovarian Cancer Xenografts

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 325
Author(s):  
Carolina Venturoli ◽  
Ilaria Piga ◽  
Matteo Curtarello ◽  
Martina Verza ◽  
Giovanni Esposito ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Metabolic Pathways ◽  
Negative Impact ◽  
Digital Pathology ◽  
Pyruvate Dehydrogenase Kinase ◽  
Ovarian Cancer Cells ◽  
Pyruvate Dehydrogenase Kinase 1

Pyruvate dehydrogenase kinase 1 (PDK1) blockade triggers are well characterized in vitro metabolic alterations in cancer cells, including reduced glycolysis and increased glucose oxidation. Here, by gene expression profiling and digital pathology-mediated quantification of in situ markers in tumors, we investigated effects of PDK1 silencing on growth, angiogenesis and metabolic features of tumor xenografts formed by highly glycolytic OC316 and OVCAR3 ovarian cancer cells. Notably, at variance with the moderate antiproliferative effects observed in vitro, we found a dramatic negative impact of PDK1 silencing on tumor growth. These findings were associated with reduced angiogenesis and increased necrosis in the OC316 and OVCAR3 tumor models, respectively. Analysis of viable tumor areas uncovered increased proliferation as well as increased apoptosis in PDK1-silenced OVCAR3 tumors. Moreover, RNA profiling disclosed increased glucose catabolic pathways—comprising both oxidative phosphorylation and glycolysis—in PDK1-silenced OVCAR3 tumors, in line with the high mitotic activity detected in the viable rim of these tumors. Altogether, our findings add new evidence in support of a link between tumor metabolism and angiogenesis and remark on the importance of investigating net effects of modulations of metabolic pathways in the context of the tumor microenvironment.

scholarly journals Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marina Stasenko ◽  
Evan Smith ◽  
Oladapo Yeku ◽  
Kay J. Park ◽  
Ian Laster ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Therapeutics ◽  
Ca 125 ◽  
Ovarian Cancer Cells ◽  
Carbohydrate Binding ◽  
Matrigel Invasion ◽  
Galectin 3

AbstractThe lectin, galectin-3 (Gal3), has been implicated in a variety of inflammatory and oncogenic processes, including tumor growth, invasion, and metastasis. The interactions of Gal3 and MUC16 represent a potential targetable pathway for the treatment of MUC16-expressing malignancies. We found that the silencing of Gal3 in MUC16-expressing breast and ovarian cancer cells in vitro inhibited tumor cell invasion and led to attenuated tumor growth in murine models. We therefore developed an inhibitory murine monoclonal anti–Gal3 carbohydrate-binding domain antibody, 14D11, which bound human and mouse Gal3 but did not bind human Galectins-1, -7, -8 or -9. Competition studies and a docking model suggest that the 14D11 antibody competes with lactose for the carbohydrate binding pocket of Gal3. In MUC16-expressing cancer cells, 14D11 treatment blocked AKT and ERK1/2 phosphorylation, and led to inhibition of cancer cell Matrigel invasion. Finally, in experimental animal tumor models, 14D11 treatment led to prolongation of overall survival in animals bearing flank tumors, and retarded lung specific metastatic growth by MUC16 expressing breast cancer cells. Our results provide evidence that antibody based Gal3 blockade may be a viable therapeutic strategy in patients with MUC16-expressing tumors, supporting further development of human blocking antibodies against Gal3 as potential cancer therapeutics.

scholarly journals Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs

2021 ◽  
Vol 7 (9) ◽  
pp. eabb0737
Author(s):  
Zhengnan Yang ◽  
Wei Wang ◽  
Linjie Zhao ◽  
Xin Wang ◽  
Ryan C. Gimple ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Phenotype ◽  
Ovarian Cancers ◽  
Novel Approach

Ovarian cancer represents a highly lethal disease that poses a substantial burden for females, with four main molecular subtypes carrying distinct clinical outcomes. Here, we demonstrated that plasma cells, a subset of antibody-producing B cells, were enriched in the mesenchymal subtype of high-grade serous ovarian cancers (HGSCs). Plasma cell abundance correlated with the density of mesenchymal cells in clinical specimens of HGSCs. Coculture of nonmesenchymal ovarian cancer cells and plasma cells induced a mesenchymal phenotype of tumor cells in vitro and in vivo. Phenotypic switch was mediated by the transfer of plasma cell–derived exosomes containing miR-330-3p into nonmesenchymal ovarian cancer cells. Exosome-derived miR-330-3p increased expression of junctional adhesion molecule B in a noncanonical fashion. Depletion of plasma cells by bortezomib reversed the mesenchymal characteristics of ovarian cancer and inhibited in vivo tumor growth. Collectively, our work suggests targeting plasma cells may be a novel approach for ovarian cancer therapy.

scholarly journals Splicing factor USP39 promotes ovarian cancer malignancy through maintaining efficient splicing of oncogenic HMGA2

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Shourong Wang ◽  
Zixiang Wang ◽  
Jieyin Li ◽  
Junchao Qin ◽  
Jianping Song ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Malignant Tumors ◽  
Splicing Factor ◽  
Ovarian Cancer Cells ◽  
Nuclear Speckles ◽  
Aberrant Expression ◽  
Intergenic Regions

AbstractAberrant expression of splicing factors was found to promote tumorigenesis and the development of human malignant tumors. Nevertheless, the underlying mechanisms and functional relevance remain elusive. We here show that USP39, a component of the spliceosome, is frequently overexpressed in high-grade serous ovarian carcinoma (HGSOC) and that an elevated level of USP39 is associated with a poor prognosis. USP39 promotes proliferation/invasion in vitro and tumor growth in vivo. Importantly, USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells. We further demonstrated that USP39 colocalizes with spliceosome components in nuclear speckles. Transcriptomic analysis revealed that USP39 deletion led to globally impaired splicing that is characterized by skipped exons and overrepresentation of introns and intergenic regions. Furthermore, RNA immunoprecipitation sequencing showed that USP39 preferentially binds to exon-intron regions near 5′ and 3′ splicing sites. In particular, USP39 facilitates efficient splicing of HMGA2 and thereby increases the malignancy of ovarian cancer cells. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor in ovarian cancer and represents a potential target for ovarian cancer therapy.

Phytochemical concentrations and biological activities of Sorghum bicolor alcoholic extracts

2016 ◽  
Vol 7 (8) ◽  
pp. 3410-3420 ◽  
Author(s):  
Vermont P. Dia ◽  
Philipus Pangloli ◽  
Lynsey Jones ◽  
Angela McClure ◽  
Anjali Patel
Keyword(s):  
Ovarian Cancer ◽  
Antioxidant Activity ◽  
Sorghum Bicolor ◽  
Cancer Cells ◽  
Biological Activities ◽  
Ovarian Cancer Cells

Sorghum alcoholic extracts exhibited antioxidant activity and capability to inhibit and chemosensitize ovarian cancer cells in vitro.

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