scholarly journals An Effective Inhibitory Strategy of Low Steady Magnetic Field on Ovarian Cancer

2021 ◽  
Author(s):  
Xiaodi Li ◽  
Yanwen Fang ◽  
Zhicai Fang ◽  
Ping Wang ◽  
Jun Zhu
Keyword(s):  
Magnetic Field ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Model ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Magnetic Intensity ◽  
Ovarian Cancer Cell Lines

Abstract To estimate the effect of a steady-state magnetic field (SMF) with low magnetic intensity gradient on the apoptosis-promoting factors related to cancer cells, we systematically select SMF with 0.2T, 0.4T and 0.6T to study their effect on different ovarian cancer lines. An in vitro cell model system about two kinds of ovarian cancer lines is established, whose viability and intracellular factors are detected by CCK-8, confocal microscopy and flow cytometry method. The results demonstrate that the apoptosis rate of ovarian cancer cells is increased with the enhancement of SMF magnetic intensity. Furthermore, we detect an increasing ROS and intracellular Ca2+ levels in ovarian cancer cells, which can be caused by SMF. The results suggest that ROS and Ca2+ levels are the main reason for the significant apoptosis of ovarian cancer cell lines in SMF. Moreover, an in vivo experiment also reveals that SMF has a strong inhibitory effect on ovarian cancer. Therefore, the inhibitory strategy is an effective, which has a great potential in the treatment of drug-resistant ovarian cancer.

scholarly journals Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel

2019 ◽  
Vol 20 (5) ◽  
pp. 1042 ◽  
Author(s):  
Apriliana Cahya Khayrani ◽  
Hafizah Mahmud ◽  
Aung Ko Ko Oo ◽  
Maram H. Zahra ◽  
Miharu Oze ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stem Cell Marker ◽  
Ovarian Cancer Cells ◽  
Cancer Therapies ◽  
Ovarian Cancer Cell Lines ◽  
Tumor Selective

Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15–20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies.

scholarly journals Combining ReACp53 with Carboplatin to Target High-Grade Serous Ovarian Cancers

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5908
Author(s):  
Adam Neal ◽  
Tiffany Lai ◽  
Tanya Singh ◽  
Neela Rahseparian ◽  
Tristan Grogan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Ovarian Cancer Cell Lines ◽  
Poor Outcomes

Ovarian malignancies are a leading cause of cancer-related death for US women. High-grade serous ovarian carcinomas (HGSOCs), the most common ovarian cancer subtype, are aggressive tumors with poor outcomes. Mutations in TP53 are common in HGSOCs, with a subset resulting in p53 aggregation and misregulation. ReACp53 is a peptide designed to inhibit mutant p53 aggregation and has been shown efficacious in targeting cancer cells in vitro and in vivo. As p53 regulates apoptosis, combining ReACp53 with carboplatin represents a logical therapeutic strategy. The efficacy of this combinatorial approach was tested in eight ovarian cancer cell lines and 10 patient HGSOC samples using an in vitro organoid drug assay, with the SynergyFinder tool utilized for calculating drug interactions. Results demonstrate that the addition of ReACp53 to carboplatin enhanced tumor cell targeting in the majority of samples tested, with synergistic effects measured in 2 samples, additivity measured in 14 samples, and antagonism measured in 1 sample. This combination was found to be synergistic in OVCAR3 ovarian cancer cells in vitro through enhanced apoptosis, and survival of mice bearing OVCAR3 intraperitoneal xenografts was extended when treated with the addition of ReACp53 to carboplatin versus carboplatin alone. Results suggest that carboplatin and ReACp53 may be a potential strategy in targeting a subset of HGSOCs.

scholarly journals WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

2020 ◽  
Author(s):  
Zi-Qing Shi ◽  
Zi-Yan Chen ◽  
Yao Han ◽  
Heng-Yan Zhu ◽  
Meng-Dan Lyu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Extracellular Signal ◽  
And Migration

Abstract Background: Wnt-inducible signaling pathway protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on the proliferation and migration of ovarian cancer cells in vitro and in vivo.Results: Immunohistochemistry and western blotting indicated that WISP2 was highly expressed in various ovarian cancer tissues and cell lines，but weakly expressed in normal ovary tissue. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells while promoting cell apoptosis and affecting the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of phosphorylated extracellular signal-related kinase (p-ERK)1/2, as well as CCAAT/enhancer-binding protein α (CEBPα) and CEPBβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP).Conclusion: WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

scholarly journals WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

2020 ◽  
Author(s):  
Zi-Qing Shi ◽  
Zi-Yan Chen ◽  
Yao Han ◽  
Heng-Yan Zhu ◽  
Meng-Dan Lyu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Growth Inhibitory ◽  
Extracellular Signal ◽  
And Migration

Abstract Background Wnt inducible signaling protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on proliferation and migration of ovarian cancer cells in vitro and in vivo . Results Immunohistochemistry and western blot results indicated that WISP2 was highly expressed in various ovarian tissues and cell lines. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells. WISP2 deletion promoted cell apoptosis and affected the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of extracellular signal-related kinase (p-ERK)1/2, as well as CEBPα and CEBPβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP). Conclusion WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

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.

scholarly journals Downregulation of TRIM27 expression inhibits the proliferation of ovarian cancer cells in vitro and in vivo

2015 ◽  
Vol 96 (1) ◽  
pp. 37-48 ◽  
Author(s):  
Yanyan Ma ◽  
Zengtao Wei ◽  
Robert C Bast ◽  
Zhanying Wang ◽  
Yan Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells

scholarly journals The role of Sox6 and Netrin-1 in ovarian cancer cell growth, invasiveness, and angiogenesis

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770550 ◽  
Author(s):  
Yi Li ◽  
Ming Xiao ◽  
Fangchun Guo
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Conditioned Medium ◽  
Umbilical Vein ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Human Umbilical Vein ◽  
Tumor Tissues

SOX6 plays important roles in cell proliferation, differentiation, and cell fate determination. It has been confirmed that SOX6 is a tumor suppressor and downregulated in various cancers, including esophageal squamous cell carcinoma, hepatocellular carcinoma, and chronic myeloid leukemia. Netrin-1 is highly expressed in various human cancers and acts as an anti-apoptotic and proangiogenic factor to drive tumorigenesis. The role of SOX6 and netrin-1 in regulating the growth of ovarian tumor cells still remains unclear. Real-time polymerase chain reaction and western blot were used to determine the SOX6 messenger RNA and protein levels, respectively, in ovarian cancer cells and tumor tissues. Stable transfection of SOX6 was conducted to overexpress SOX6 in PA-1 and SW626 cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Invasion of ovarian cancer cells and migration of human umbilical vein endothelial cells were confirmed by Transwell assays. To overexpress netrin-1, ovarian cancer cells with SOX6 restoration was transduced with netrin-1 lentiviral particles. PA-1 xenografts in a nude mice model were used to conduct in vivo evaluation of the role of SOX6 and its relationship with netrin-1 in tumor growth and angiogenesis. In this study, we found significantly reduced SOX6 levels in PA-1, SW626, SK-OV-3, and CaoV-3 ovarian cancer cell lines and human tumor tissues in comparison with normal human ovarian epithelial cells or matched non-tumor tissues. SOX6 overexpression by stable transfection dramatically inhibited proliferation and invasion of PA-1 and SW626 cells. Also, conditioned medium from PA-1 and SW626 cells with SOX6 restoration exhibited reduced ability to induce human umbilical vein endothelial cells migration and tube formation compared with conditioned medium from the cells with transfection control. Furthermore, an inverse relationship between SOX6 and netrin-1 expression was observed in PA-1 and SW626 cells. Overexpression of netrin-1 in ovarian cancer cells with forced SOX6 expression remarkably abrogated the inhibitory effect of SOX6 on proliferation, invasion of the cells, and tumor xenograft growth and vascularity in vivo. Human umbilical vein endothelial cell migration and tube formation were enhanced in the conditioned medium from the ovarian cancer cells transduced with netrin-1 lentivirus particles. Our observations revealed that SOX6 is a tumor suppressor in ovarian cancer cells, and SOX6 exerts an inhibitory effect on the proliferation, invasion, and tumor cell-induced angiogenesis of ovarian cancer cells, whereas nerin-1 plays an opposite role and its expression is inversely correlated with SOX6. Moreover, our findings suggest a new role of SOX6 and netrin-1 for understanding the progression of ovarian cancer and have the potential for the development of new diagnosis and treatment strategies for ovarian cancer.

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