Docosahexaenoic Acid Modulates Invasion and Metastasis of Human Ovarian Cancer via Multiple Molecular Pathways

ObjectiveWe investigated the effect of docosahexaenoic acid (DHA) on the invasion and metastasis of ovarian cancer cells (A2780, HO8910, and SKOV-3).MethodsCytotoxicity assay was performed to determine the optimal doses of DHA in this experiment. The effects of DHA on invasion ability were assessed by invasion assay. The expressions of messenger RNA and/or proteins associated with invasion or metastasis were detected by quantitative Real Time-Polymerase Chain Reaction or Western blot. The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish.ResultsDocosahexaenoic acid and α-linolenic acid could reduce the cell vitalities in dose-dependent manner. However, DHA inhibited the invasion and metastasis of ovarian cancer cells, but α-linolenic acid did not (**P < 0.01). Docosahexaenoic acid could downregulate the expressions of WAVE3, vascular endothelial cell growth factor, and MMP-9, and upregulate KISS-1, TIMP-1, and PPAR-γ, which negatively correlated with cell invasion and metastasis (*P < 0.05). Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01).ConclusionsDocosahexaenoic acid inhibited the invasion and metastasis of ovarian cancer cells in vitro and in vivo through the modulation of NF-κB signaling pathway, suggesting that DHA is a promising candidate for ovarian cancer therapy.

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UBE2S promotes the progression and Olaparib resistance of ovarian cancer through Wnt/β-catenin signaling pathway

Journal of Ovarian Research ◽

10.1186/s13048-021-00877-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Wenjing Hu ◽

Min Li ◽

Youguo Chen ◽

Xinxian Gu

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Xenograft Model ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Cancer Proliferation ◽

Skov3 Cells

Abstract Background Ovarian cancer is the most lethal gynecologic malignancy worldwide. Olaparib, an inhibitor of poly (ADP-ribose) polymerase (PARP), is becoming widely used in ovarian cancer treatment. The overall survival of ovarian cancer has not been significantly changed over the past decades and ovarian cancer has become increasingly resistant to the Olaparib. Ubiquitin-conjugating enzyme E2S (UBE2S) has been proved to promote malignant behaviors in many cancers. However, the function of UBE2S in the development and Olaparib resistance of ovarian cancer are unclear. Materials and methods In this study, we detected the expression of UBE2S in normal fallopian tube (FT) and HGSOC tissues. A2780 and SKOV3 cells were stably transfected with PCMV-UBE2S, PCMV-UBE2S-C95S, UBE2S shRNAs, and negative controls. The CCK8 assay and clonogenic assay were conducted to analyze ovarian cancer proliferation and Olaparib resistance. The transwell assay was performed to determine the migration and invasion of ovarian cancer cells. The relative protein levels of the Wnt/β-catenin signaling pathway were tested using western blot. The ovarian cancer cells were treated with XAV-939 to investigate the role of Wnt/β-catenin signaling pathway in Olaparib resistance. Moreover, we repeated some above procedures in the xenograft model. Results The results demonstrated that UBE2S was highly upregulated in HGSOC and that high UBE2S expression was correlated with poor outcomes in HGSOC. UBE2S promoted ovarian cancer proliferation and drived the migration and invasion of ovarian cancer cells. UBE2S activated the Wnt/β-catenin signaling pathway in ovarian cancer resulting in Olaparib resistance in vitro and in vivo. Furthermore, UBE2S enhanced the proliferation and Olaparib resistance of ovarian cancer in its enzymatic activity dependent manner. Conclusions These data suggest a possible molecular mechanism of proliferation and metastasis of ovarian cancer and highlight the potential role of UBE2S as a therapeutic target in ovarian cancer.

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Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis

Journal of Ovarian Research ◽

10.1186/s13048-021-00775-3 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Huan Lu ◽

Guanlin Zheng ◽

Xiang Gao ◽

Chanjuan Chen ◽

Min Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cancer Cells ◽

Rna Binding ◽

Erk Signaling ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Vacuolar Protein

Abstract Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

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

Marine Drugs ◽

10.3390/md18050261 ◽

2020 ◽

Vol 18 (5) ◽

pp. 261 ◽

Cited By ~ 1

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.

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224 A GROWTH OF HUMAN BG-1 CANCER CELLS EXPRESSING ESTROGEN RECEPTORS WAS ENHANCED BY SYNTHETIC PYRETHROIDS, LAMBDA-CYHALOTHRIN AND CYPERMETHRIN, VIA AN ESTROGEN RECEPTOR-DEPENDENT SIGNALING PATHWAY

Reproduction Fertility and Development ◽

10.1071/rdv27n1ab224 ◽

2015 ◽

Vol 27 (1) ◽

pp. 201 ◽

Cited By ~ 1

Author(s):

C.-W. Kim ◽

R.-E. Go ◽

K.-C. Choi

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Mtt Assay ◽

Ovarian Cancer Cells ◽

Transcriptional Level ◽

Synthetic Pyrethroids ◽

Dependent Manner ◽

Rt Pcr ◽

Pyrethroid Insecticides ◽

Lambda Cyhalothrin

Synthetic pyrethroids (SP) are the most common pesticides in recent use, which are used as indoor pest control. The widespread use of SPs has resulted in extensive exposure to wildlife and human. Recently some SPs are suspected as endocrine disrupting chemicals (EDC) and have been assessed for their potential estrogenicity by various assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LCT) and cypermethrin (CP), the most commonly used pyrethroid insecticides in Korea, using BG-1 ovarian cancer cells expressing oestrogen receptors (ER). To evaluate the estrogenic activities of two SPs, LCT and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT–PCR). In MTT assay, LCT (10–6 M) and CP (10–5 M) significantly induced the growth of BG-1 cancer cells, 1.61 ± 0.1 and 1.45 ± 0.06 times, respectively, as 17β-oestradiol (E2, 10–9 M, 2.73 ± 0.25 times) did. LCT or CP-induced cell growth was reversed to a control level (DMSO) by addition of ICI 182 720 (10–8 M), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT–PCR results showed that transcriptional level of ERα expression was significantly down-regulated by LCT and CP as in case of E2. Taken together, these results indicate that LCT and CP may possess estrogenic potentials to stimulate ovarian cancer cells expressing ERs via an ER-dependent manner, and these collective results confirm the carcinogenicity of these SP, LCT and CP, in ER-positive cells or tissues.

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

Cells ◽

10.3390/cells8070644 ◽

2019 ◽

Vol 8 (7) ◽

pp. 644 ◽

Cited By ~ 5

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.

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Mechanism of Cepharanthine Cytotoxicity in Human Ovarian Cancer Cells

Planta Medica ◽

10.1055/a-0706-7503 ◽

2018 ◽

Vol 85 (01) ◽

pp. 41-47 ◽

Cited By ~ 5

Author(s):

Vilawan Payon ◽

Chanaporn Kongsaden ◽

Wannarasmi Ketchart ◽

Apiwat Mutirangura ◽

Piyanuch Wonganan

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cell ◽

Apoptotic Cell ◽

Chemotherapeutic Agents ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Ovarian Cancer Cell Lines ◽

Underlying Mechanisms

AbstractCepharanthine (CEP), a medicinal product derived from Stephania cephalantha Hayata, possesses a potent cytotoxicity against several types of cancers. Recently, we have found that CEP could efficiently inhibit the growth of mutated p53 colon cancer cells, which are often resistant to commonly used chemotherapeutic agents. In this study, we evaluated the cytotoxic effect and the underlying mechanisms of CEP on both chemosensitive CaOV-3 and chemoresistant OVCAR-3 ovarian cancer cell lines. The present study demonstrated that CEP significantly inhibited the growth of CaOV-3 and OVCAR-3 cells in a time- and concentration-dependent manner. CEP arrested CaOV-3 and OVCAR-3 cells in the G1 phase and S phase of cell cycle, respectively. Western blot analysis demonstrated that CEP markedly increased the expression of p21Waf1 protein and decreased the expression of cyclins A and D proteins in both CaOV-3 and OVCAR-3 cells. Additionally, CEP triggered apoptotic cell death in OVCAR-3 cells. Taken together, the above results suggest that CEP is a promising anticancer drug for ovarian cancer.

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Critical role of SEMA5A expression in invasion and metastasis of ovarian cancer cell

American Journal of BioMedicine ◽

10.18081/2333-5106/014-04/247-259 ◽

2014 ◽

Vol 2 (4) ◽

pp. 247-259

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Critical Role ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Cancer Tissue ◽

Invasion And Metastasis

Semaphorins are a large family of genes involved in the development and morphogenesis of the nervous system. SEMA5A has been reported as a bi-functional molecule, acting as both oncogene and tumor suppressor in different types of cancer. High expression levels of SEMA5A and its receptor, Plexin-B3, were associated with aggressiveness in pancreatic and prostate cancers. Our previous study in ovarian cancer metastasis indicates that FAK knock-down can suppress ovarian cancer cells migration and invasion. We hypothesized that SEMA5A expression promotes ovarian cancer invasion and metastasis. We investigated the expression of SEMA5A in patients with metastatic ovarian cancer (n = 43), localized tumor (n = 37) and normal ovarian tissue (n = 12) from non-malignant diseases as control with different histopathological characteristics. For Silencing of SEMA5A in vitro, we treated human ovarian cancer cells (OVCAR-3, A2780/CP70) with miR-27a and miR-27b. We observed significantly higher expression of SEMA5A protein (P= 0.001) in metastatic ovarian cancer tissue associated with poor overall survival outcomes compared to localized ovarian cancer and control. In vitro silencing of SEMA5A reduced migration and invasion of ovarian cancer cell. Our data offer opportunities for the therapeutic modulation and biomarker of metastatic ovarian cancer.

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Aurora-A induces cell survival and chemoresistance by activation of Akt through a p53-dependent manner in ovarian cancer cells

International Journal of Cancer ◽

10.1002/ijc.22154 ◽

2006 ◽

Vol 119 (10) ◽

pp. 2304-2312 ◽

Cited By ~ 93

Author(s):

Hua Yang ◽

Lili He ◽

Patricia Kruk ◽

Santo V. Nicosia ◽

Jin Q. Cheng

Keyword(s):

Ovarian Cancer ◽

Cell Survival ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Aurora A

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Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/350239 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Chien-Chih Ou ◽

Yuan-Wu Chen ◽

Shih-Chung Hsu ◽

Huey-Kang Sytwu ◽

Shih-Hurng Loh ◽

...

Keyword(s):

Ovarian Cancer ◽

Protein Expression ◽

Tumor Growth ◽

Cancer Cells ◽

Promoter Activity ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Ki 67 ◽

Nih3t3 Cells ◽

Her2 Protein

Triptolide (TPL) inhibits the proliferation of a variety of cancer cells and has been proposed as an effective anticancer agent. In this study, we demonstrate that TPL downregulates HER2 protein expression in oral, ovarian, and breast cancer cells. It suppresses HER2 protein expression in a dose- and time-dependent manner. Transrepression of HER2 promoter activity by TPL is also observed. The interacting site of TPL on the HER2 promoter region is located between −207 and −103 bps, which includes a putative binding site for the transcription factor NF-κB. Previous reports demonstrated that TPL suppresses NF-κB expression. We demonstrate that overexpression of NF-κB rescues TPL-mediated suppression of HER2 promoter activity and protein expression in NIH3T3 cells and ovarian cancer cells, respectively. In addition, TPL downregulates the activated (phosphorylated) forms of HER2, phosphoinositide-3 kinase (PI3K), and serine/threonine-specific protein kinase (Akt). TPL also inhibits tumor growth in a mouse model. Furthermore, TPL suppresses HER2 and Ki-67 expression in xenografted tumors based on an immunohistochemistry (IHC) assay. These findings suggest that TPL transrepresses HER2 and suppresses the downstream PI3K/Akt-signaling pathway. Our study reveals that TPL can inhibit tumor growth and thereby may serve as a potential chemotherapeutic agent.

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Difluoromethylornithine Induces Apoptosis through Regulation of AP-1 Signaling via JNK Phosphorylation in Epithelial Ovarian Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms221910255 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10255

Author(s):

Woo Yeon Hwang ◽

Wook Ha Park ◽

Dong Hoon Suh ◽

Kidong Kim ◽

Yong Beom Kim ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Epithelial Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Irreversible Inhibitor ◽

Protein Levels ◽

Bax Protein ◽

Apoptotic Effects

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has promising activity against various cancers and a tolerable safety profile for long-term use as a chemopreventive agent. However, the anti-tumor effects of DFMO in ovarian cancer cells have not been entirely understood. Our study aimed to identify the effects and mechanism of DFMO in epithelial ovarian cancer cells using SKOV-3 cells. Treatment with DFMO resulted in a significantly reduced cell viability in a time- and dose-dependent manner. DFMO treatment inhibited the activity and downregulated the expression of ODC in ovarian cancer cells. The reduction in cell viability was reversed using polyamines, suggesting that polyamine depletion plays an important role in the anti-tumor activity of DFMO. Additionally, significant changes in Bcl-2, Bcl-xL, Bax protein levels, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase were observed, indicating the apoptotic effects of DFMO. We also found that the effect of DFMO was mediated by AP-1 through the activation of upstream JNK via phosphorylation. Moreover, DFMO enhanced the effect of cisplatin, thus showing a possibility of a synergistic effect in treatment. In conclusion, treatment with DFMO alone, or in combination with cisplatin, could be a promising treatment for ovarian cancer.

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