Nanog-mediated stem cell properties is critical for MBNL3 associated paclitaxel resistance of ovarian cancer

2021 ◽  
Author(s):  
Xueqin Sun ◽  
Xinghua Diao ◽  
Xiaolin Zhu ◽  
Xuexue Yin ◽  
Guangying Cheng
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Drug Targets ◽  
Xenograft Model ◽  
Underlying Mechanism ◽  
Multi Drug Resistance ◽  
Ovarian Cancer Cells ◽  
Loss Of Function ◽  
Cancer Management ◽  
Nanog Gene

Abstract Paclitaxel (PTX) is the standard first-line treatment of ovarian cancer, but its efficacy is limited by multi-drug resistance. Therefore, it is crucial to identify effective drug targets to facilitate PTX-sensitivity for ovarian cancer treatment. Seventy PTX-administrated ovarian cancer patients were recruited in this study for gene expression and survival rate analyses. Muscleblind-like-3 (MBNL3) gain- and loss-of-function experiments were carried out in ovarian cancer cells (parental and PTX-resistant) and xenograft model. Cancer cell viability, apoptosis, spheroids formation, Nanog gene silencing were examined and conducted to dissect the underlying mechanism of MBNL3-mediated PTX-resistance. High expression of MBNL3 was positively correlated with PTX-resistance and poor prognosis of ovarian cancer. MBNL3 increased cell viability and decreased apoptosis in ovarian stem-like cells, through up-regulating Nanog. This study suggests the MBNL3-Nanog axis is a therapeutic target for the treatment of PTX-resistance in ovarian cancer management.

Lupeol Inhibits Proliferation and Promotes Apoptosis of Ovarian Cancer Cells by Inactivating Phosphoinositide-3-Kinase/Protein Kinase B/ Mammalian Target of Rapamycin Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 206-210
Author(s):  
Feng Chen ◽  
Bei Zhang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Protein Kinase ◽  
Cell Viability ◽  
Cancer Cells ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Ovarian Cancer Cells ◽  
Phosphoinositide 3 Kinase

Lupeol exhibits multiple pharmacological activities including, anticancerous, anti-inflammatory, and antioxidant. The aim of this study was to explore the anticancerous activity of lupeol on ovarian cancer cells and examine its mechanism of action. To this end, increasing concentrations of lupeol on cell viability, cell cycle, and apoptosis in Caov-3 cells were evaluated. Lupeol inhibited cell viability, induced G1 phase arrest in cell cycle, increased cell apoptosis, and inhibited the ratio of phospho-Akt/protein kinase B and phospho-mammalian target of rapamycin/mammalian target of rapamycin. In conclusion, these data suggest that lupeol may play a therapeutic role in ovarian cancer.

Gemcitabine Nanoparticles Improve the Activity of Ovarian Cancer Cells by Inhibiting CA-125 and Apoptosis-Related Proteins

2021 ◽  
Vol 11 (7) ◽  
pp. 1400-1405
Author(s):  
Sisi Yi ◽  
Chen Feng ◽  
Xiaohua Hu
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Release Rate ◽  
Inhibitory Action ◽  
Encapsulation Efficiency ◽  
Slow Release ◽  
Drug Loading ◽  
Ca 125 ◽  
Ovarian Cancer Cells ◽  
Related Proteins

In recent years, the risk of ovarian cancer (OC) has become increasingly prevalent. Gemcitabine (GE) provides excellent inhibitory action on some solid tumors, but how it affects OC remains elusive. In the present research, we prepared GE nanoparticles (GEN) and analyzed OC cell viability under its intervention, hoping to conceive novel ideas for future clinical treatment of OC. Through experiments, we observed that the encapsulation efficiency and drug loading of GEN were observably higher than those of GE alone, and the release rate presented a stable slow release state. Under GEN intervention, the viability of OC cells was decreased, the apoptosis rate was elevated, and the apoptosis-related proteins were activated, while CA-125 was suppressed. Therefore, we can see that GEN exert favorable inhibitory action on OC cell viability, whose mechanism may be achieved through activating apoptosis-related proteins and inhibiting CA-125, which may be a new scheme for OC treatment in the future.

GRP137 promotes cell proliferation and metastasis through regulation of the PI3K/AKT pathway in human ovarian cancer

2018 ◽  
Vol 104 (5) ◽  
pp. 330-337 ◽  
Author(s):  
Li-qian Zhang ◽  
Su-qing Yang ◽  
Xiang-dong Qu ◽  
Xian-jun Chen ◽  
Hong-sheng Lu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
G Protein ◽  
Biological Activities ◽  
Xenograft Model ◽  
Akt Pathway ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
G Protein Coupled Receptor ◽  
Skov3 Cells ◽  
G Protein Coupled

Purpose: Ovarian cancer is one of the leading causes of death for women worldwide. The present study aims to investigate the role of G protein-coupled receptor 137 (GPR137) in the biological activities of ovarian cancer cells. Methods: (QUERY: Please supply Methods for Abstract) Results: G protein-coupled receptor 137 was highly expressed in clinical ovarian cancer tissues and exhibited the highest protein levels in SKOV3 cells and OVCAR3 cells. Knockdown of GPR137 caused significant decreases in cell proliferative rates and colony formation abilities in SKOV3 cells and OVCAR3 cells and also inhibited the in vivo tumorigenesis in a xenograft model. It was observed that knockdown of GPR137 inhibited cell motility by up to 40% in SKOV3 cells and approximately 65% in OVCAR3 cells in wound-healing assay. Cell migration abilities were consistently inhibited by 68.2% in SKOV3 cells and 59.3% in OVCAR3 cells, whereas cell invasion abilities were inhibited by 64.0% and 74.2% in SKOV3 and OVCAR3 cells, respectively, after knockdown of GPR137. When GPR137 was depleted, epithelial markers were increased, while mesenchymal markers decreased. Conclusions: Our data suggest that GPR137 plays pro-oncogenic roles in ovarian cancer via regulation of the PI3K/AKT pathway. These observations might pave new insights into therapeutic strategies against human ovarian cancer.

scholarly journals Fucosterol Suppresses the Progression of Human Ovarian Cancer by Inducing Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

Marine Drugs ◽  
2020 ◽  
Vol 18 (5) ◽  
pp. 261 ◽  
Author(s):  
Hyocheol Bae ◽  
Jin-Young Lee ◽  
Gwonhwa Song ◽  
Whasun Lim
Keyword(s):  
Ovarian Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Anticancer Properties

Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared to traditional chemotherapy, natural compounds can overcome drug resistance with lower side effects. Fucosterol, a phytosterol present in brown algae, reportedly possesses many bioactive effects, including anticancer properties. However, the anticancer effects of fucosterol in ovarian cancer remain unexplored. Therefore, we investigated the effects of fucosterol on progression in human ovarian cancer cells. Fucosterol inhibited cell proliferation and cell-cycle progression in ovarian cancer cells. Additionally, fucosterol regulated the proliferation-related signaling pathways, the production of reactive oxygen species, mitochondrial function, endoplasmic reticulum stress, angiogenesis, and calcium homeostasis. Moreover, it decreased tumor formation in a zebrafish xenograft model. These results indicate that fucosterol could be used as a potential therapeutic agent in ovarian cancer.

The application of metabolomics in ovarian cancer management: a systematic review

2020 ◽  
pp. ijgc-2020-001862
Author(s):  
Yousra Ahmed-Salim ◽  
Nicolas Galazis ◽  
Timothy Bracewell-Milnes ◽  
David L Phelps ◽  
Benjamin P Jones ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
English Language ◽  
Global Analysis ◽  
Clinical Care ◽  
Underlying Mechanism ◽  
Phospholipid Metabolism ◽  
Fast Method ◽  
Cellular Processes ◽  
Cancer Management

Metabolomics, the global analysis of metabolites in a biological specimen, could potentially provide a fast method of biomarker identification for ovarian cancer. This systematic review aims to examine findings from studies that apply metabolomics to the diagnosis, prognosis, treatment, and recurrence of ovarian cancer. A systematic search of English language publications was conducted on PubMed, Science Direct, and SciFinder. It was augmented by a snowball strategy, whereby further relevant studies are identified from reference lists of included studies. Studies in humans with ovarian cancer which focus on metabolomics of biofluids and tumor tissue were included. No restriction was placed on the time of publication. A separate review of targeted metabolomic studies was conducted for completion. Qualitative data were summarized in a comprehensive table. The studies were assessed for quality and risk of bias using the ROBINS-I tool. 32 global studies were included in the main systematic review. Most studies applied metabolomics to diagnosing ovarian cancer, within which the most frequently reported metabolite changes were a down-regulation of phospholipids and amino acids: histidine, citrulline, alanine, and methionine. Dysregulated phospholipid metabolism was also reported in the separately reviewed 18 targeted studies. Generally, combinations of more than one significant metabolite as a panel, in different studies, achieved a higher sensitivity and specificity for diagnosis than a single metabolite; for example, combinations of different phospholipids. Widespread metabolite differences were observed in studies examining prognosis, treatment, and recurrence, and limited conclusions could be drawn. Cellular processes of proliferation and invasion may be reflected in metabolic changes present in poor prognosis and recurrence. For example, lower levels of lysine, with increased cell invasion as an underlying mechanism, or glutamine dependency of rapidly proliferating cancer cells. In conclusion, this review highlights potential metabolites and biochemical pathways which may aid the clinical care of ovarian cancer if further validated.

PLGA-nanoparticles loaded with a thiosemicarbazone derived palladium(ii) complex as a potential agent to new formulations for human ovarian carcinoma treatment

2020 ◽  
Vol 44 (35) ◽  
pp. 14928-14935
Author(s):  
Carolina G. Oliveira ◽  
Luciana F. Dalmolin ◽  
R. T. C. Silva ◽  
Renata F. V. Lopez ◽  
Pedro I. S. Maia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Ovarian Carcinoma ◽  
Cancer Cells ◽  
Plga Nanoparticles ◽  
Cytotoxic Agent ◽  
Ovarian Cancer Cells ◽  
Ovarian Cell ◽  
Encapsulation Process ◽  
Human Ovarian Carcinoma

The encapsulation process of the PdII complex [PdCl(PPh3)(PrCh)], a promising cytotoxic agent on ovarian cancer cells, in PLGA polymer was studied. The cytotoxicity results showed that the formulation led to a significant reduction of the ovarian cell viability (80% at 1 μM).

scholarly journals CD133 Targeted PVP/PMMA Microparticle Incorporating Levamisole for the Treatment of Ovarian Cancer

Polymers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 479
Author(s):  
Yu-Chi Wang ◽  
Meng-Yi Bai ◽  
Ying-Ting Yeh ◽  
Sung-Ling Tang ◽  
Mu-Hsien Yu
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Model ◽  
Drug Carrier ◽  
Matrix Material ◽  
Free Form ◽  
Ovarian Cancer Cells ◽  
Dose Dependent

Levamisole (LEVA) is used to treat worm infections, but it can also inhibit cancer cell growth by inhibiting the aldehyde dehydrogenase pathway. Therefore, here, we developed a drug carrier targeting CD133, a biomarker overexpressed in ovarian cancer cells. The particle structure and cytotoxicity of the prepared LEVA-containing particles—called LEVA/PVP/PMMA microparticles (MPs) (because it used matrix material polyvinylpyrrolidone (PVP) and poly(methylmethacrylate) (PMMA))—were investigated in the ovarian cancer cell lines SKOV-3 and CP70. The particle size of the MPs was determined to be 1.0–1.5 µm and to be monodispersed. The hydrophilic property of PVP created a porous MP surface after the MPs were soaked in water for 20 min, which aided the leaching of the hydrophilic LEVA out of the MPs. The encapsulation efficiency of LEVA/PVP/PMMA MPs could reach up to 20%. Free-form LEVA released 50% of drugs in <1 h and 90% of drugs in 1 day, whereas the drug release rate of LEVA/PVP/PMMA MPs was much slower; 50% released in 4 h and only 70% of drugs released in 1 day. In the in vitro cell model test, 5 mM free-form LEVA and 0.1 g/mL CD133 targeted LEVA/PVP/PMMA MPs reduced SKOV-3 cell viability by 60%; 0.1 g/mL LEVA/PVP/PMMA MPs was equivalent to a similar dosage of the free drug. In addition, the cytotoxicity of CD133-conjugated LEVA/PVP/PMMA MPs shows a different cytotoxicity response toward cell lines. For SKOV-3 cells, treatment with free-form LEVA or CD133-conjugated LEVA/PVP/PMMA MPs exerted dose-dependent cytotoxic effects on SKOV-3 cell viability. However, CD133-conjugated LEVA/PVP/PMMA MPs demonstrated no significant dose-dependent cytotoxic efficacy toward CP70 cells.

scholarly journals An Ex-Vivo Culture System of Ovarian Cancer Faithfully Recapitulating the Pathological Features of Primary Tumors

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 644 ◽  
Author(s):  
Ghani ◽  
Dendo ◽  
Watanabe ◽  
Yamada ◽  
Yoshimatsu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Xenograft Model ◽  
Culture Method ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Primary Tumors

The success rate of establishing human cancer cell lines is not satisfactory and the established cell lines often do not preserve the molecular and histological features of the original tissues. In this study, we developed a novel culture method which can support proliferation of almost all primary epithelial ovarian cancer cells, as well as primary normal human oviductal epithelial cells. Cancer cells from fresh or frozen specimens were enriched by the anti-EpCAM antibody-conjugated magnetic beads, plated on Matrigel-coated plate and cultivated under the optimized culture conditions. Seventeen newly established ovarian cancer cell lines, which included all four major histotypes of ovarian cancer, were confirmed to express histotype-specific markers in vitro. Some of the cell lines from all the four histotypes, except mucinous type, generated tumors in immune-deficient mice and the xenograft tumor tissues recapitulated the corresponding original tissues faithfully. Furthermore, with poorly tumorigenic cell lines including mucinous type, we developed a novel xenograft model which could reconstruct the original tissue architecture through forced expression of a set of oncogenes followed by its silencing. With combination of the novel culture method and cell-derived xenograft system, virtually every epithelial ovarian cancer can be reconstituted in mice in a timely fashion.

scholarly journals Anticancer Effects of Cordyceps Militaris Extract in Human Ovarian Cancer Cells via ADORA2B (P05-012-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
So Young Yoon ◽  
Soo Jung Park ◽  
Yoon Jung Park
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cordyceps Militaris ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Camp Production ◽  
Anticancer Effects ◽  
Sch 58261

Abstract Objectives The study was aimed to determine anticancer effects of Cordyceps militaris extract (CME) and its major bioactive compound, cordycepin, in human ovarian cancer cells, and to identify their putative molecular mechanism mediated by adenosine receptors (ADORAs). Methods CME was prepared in 50% ethanol solution. LC-MS was used for quantification and Q-TOF MS for qualifying bioactive compounds in CME. MTT assay was performed for cell viability in A2780, SKOV-3, TOV112D, and OVCAR-3 human ovarian cancer cell lines. cAMP response element (CRE)-luciferase reporter gene assays were used to determine whether antitumorigenic effect of CME/cordycepin is based on adenosine derivatives. Additionally, the involvement of ADORA signaling pathway was measured using with ADORA2A antagonist SCH 58261 and ADORA2B antagonist PSB 603. Results Cordycepin concentrations of CME was 21.8%. CME was effective to reduce cell viability in A2780 and OVCAR-3 with IC50 115.2 μg/ml and 155.94 μg/ml respectively, while SKOV-3 and TOV112D were relatively resistant to CME. cAMP production was significantly increased by treatment with cordycepin and, lesser extent, with CME. Among the four types of ADORAs, ADORA2A and 2B showed relatively higher expression levels in ovarian cancer cells. The cAMP production by CME was ameliorated by PSB 603, not SCH 58261, treatment. Conclusions CME and cordycepin have anticancer effects in human ovarian cancer cells via ADORA2B-cAMP pathway. Funding Sources NRF of Korea (2017R1D1A1B03034936 & 22A20130012143) and Health Fellowship Foundation.

scholarly journals Lysine-specific demethylase KDM3A regulates ovarian cancer stemness and chemoresistance

Oncogene ◽  
2016 ◽  
Vol 36 (11) ◽  
pp. 1537-1545 ◽  
Author(s):  
S Ramadoss ◽  
S Sen ◽  
I Ramachandran ◽  
S Roy ◽  
G Chaudhuri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Target Genes ◽  
Kinase Inhibitor ◽  
P53 Protein ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Cancer Stemness ◽  
Sox2 Expression

Abstract Ovarian cancer is the leading cause of death among all gynecological malignancies due to the development of acquired chemoresistance and disease relapse. Although the role of cancer stem cells (CSCs), a subset of tumor cells with the self-renewal and differentiation capabilities, in therapeutic resistance is beginning to be better understood, the significance of epigenetic regulatory mechanisms responsible for integrating the stemness with drug resistance remain poorly understood. Here we identified that lysine demethylase KDM3A as a critical regulator of ovarian cancer stemness and cisplatin resistance by inducing the expressions of pluripotent molecules Sox2 and Nanog and anti-apoptotic B-cell lymphoma 2 (Bcl-2), respectively. In addition, KDM3A induces ovarian cancer growth while antagonizing cellular senescence by repressing the expression of cyclin-dependent kinase inhibitor, p21Waf1/Cip1. The underlying mechanism of the noted biological processes include KDM3A-mediated stimulation of Sox2 expression, and demethylating p53 protein and consequently, modulating its target genes such as Bcl-2 and p21Waf1/Cip1 expression. Consistently, KDM3A depletion inhibited the growth of subcutaneously implanted cisplatin-resistant human ovarian cancer cells in athymic nude mice. Moreover, KDM3A is abundantly expressed and positively correlated with Sox2 expression in human ovarian cancer tissues. In brief, our findings reveal a novel mechanism by which KDM3A promotes ovarian CSCs, proliferation and chemoresistance and thus, highlights the significance of KDM3A as a novel therapeutic target for resistant ovarian cancer.

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