Puerarin Restrains the Malignant Progression of Ovarian Cancer Cells via Regulating P53 and PTEN expressions

Abstract Objective: Puerarin has been proven to treat diverse cancers, but its function on ovarian cancer (OC) is still blurry and needs further research.Methods: After OC cells were treated with 10, 20, 40, 80, or 160 μg/mL pue, cell vitality, colony number, apoptosis, the positive expression of P53, migration, and invasion were examined by cell function experiments, TUNEL staining, and immunofluorescence. P53, P21, PTEN, FGF1, GLI2, and ERK1/2-NF-κB pathway-related marker expressions were examined by western blot. Results: Pue weakened the OC cell vitality, colony number, and the positive expression of P53 but enhanced apoptosis in a dose-dependent manner. Next, we discovered that pue enhanced the P53, P21, PTEN, and GLI2 levels but restrained the FGF1 level. Pue also alleviated the OC cell migration and invasion activity. We also confirmed that pue weakened the ERK1/2-NF-κB pathway-related marker expressions.Conclusion: Puerarin restrained the OC progression via modulating P53 and PTEN expressions.

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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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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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Ligustrazine inhibits the proliferation and migration of ovarian cancer cells via regulating miR-211

Bioscience Reports ◽

10.1042/bsr20200199 ◽

2021 ◽

Vol 41 (1) ◽

Author(s):

Hairong Zhang ◽

Shichao Ding ◽

Lei Xia

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Anti Cancer ◽

And Migration ◽

The Impact ◽

Proliferation And Migration

Abstract Ovarian cancer (OC) is a commonly diagnosed female cancer. Ligustrazine (LSZ), a natural compound, has been reported to exert anti-cancer activity, although the mechanisms underlying the anti-cancer effects are not clear. The present study investigated the impact of LSZ on cell proliferation and migration by regulating microRNA-211 (miR-211) expression using the human ovarian cancer SK-OV-3 and OVCAR-3 cell lines. OC cells were treated with 0, 0.5, 1, and 2 mM LSZ, and quantitative real-time PCR was utilized to measure miR-211 levels in SK-OV-3 and OVCAR-3 cells with different treatment. Moreover, to further confirm the roles of miR-211 in LSZ induced anti-tumor effects, miR-211 expression was inhibited by transfection of miR-211 inhibitors in SK-OV-3 cells. Cell proliferation of transfected cells was evaluated using the CCK-8 and colony formation assay. The scratch assay was employed to assess cell migration and transwell assay was performed for evaluating the cell invasion. Protein levels of epithelial–mesenchymal transition (EMT) markers were determined by Western blotting. We found that LSZ inhibited the viability, proliferation, migration and invasion ability of SK-OV-3 and OVCAR-3 cells in a dose-dependent manner; moreover, LSZ could significantly increase the expression of miR-211 in both SK-OV-3 and OVCAR-3, and knockdown of miR-211 in SK-OV-3 cells partially abrogated the anti-tumor behavior of LSZ by promoting the viability, proliferation, migration, invasion and EMT of SK-OV-3 cells. Thus, we found that LSZ can inhibit the proliferation and migration of OC cells via regulating miR-211. Our study suggests that LSZ might be a potential and effective treatment for OC.

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Tea polyphenol decreased growth and invasion in human ovarian cancer cells

European Journal of Inflammation ◽

10.1177/1721727x16674480 ◽

2016 ◽

Vol 14 (3) ◽

pp. 206-211

Author(s):

Qin Huang ◽

Ting Du ◽

Qiu-Xia Qu

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Therapeutic Strategy ◽

Ovarian Cancer Cells ◽

Cyclin D ◽

Dependent Manner ◽

Tea Polyphenol ◽

Anti Cancer ◽

Dose Dependent

Tea polyphenols (TP) are functional substances present in tea, which is one of the most promising preventive agents for cancer. This study was carried out to analyze the effects of TP on the ovarian cancer cells and possible mechanisms involved. TP led to inhibition of cell growth in a time- and dose-dependent manner, and promoted entry into the apoptosis-phase of the cell cycle. TP also decreased the invasion of ovarian cancer cells in vitro. In addition, TP treatment upregulated the mRNA expressions rate of Bax/Bcl-2 and downregulated Cyclin D and MMP2 mRNA expressions. Taken together, our data highlight that TP could be a potential therapeutic strategy for ovarian cancer. These findings also suggested that oncogens are involved in the anti-cancer effects of TP.

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Moderate Static Magnet Fields Suppress Ovarian Cancer Metastasis via ROS-Mediated Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/7103345 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Chao Song ◽

Biao Yu ◽

Junjun Wang ◽

Xinmiao Ji ◽

Lei Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Metastasis ◽

Physical Method ◽

Superconducting Magnet ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Patient Death

Metastasis is the leading cause of cancer patient death, which is closely correlated with reactive oxygen species (ROS) levels. It is well known that the effects of ROS on tumors are diverse, depending on ROS concentration and cell type. We found that ovarian cancer cells have significantly lower levels of ROS than normal ovarian cells. Moreover, increased ROS levels in ovarian cancer cells can substantially inhibit their migration and invasion ability. Furthermore, the results show that moderate static magnetic field (SMF) can inhibit ovarian cancer cell migration, invasion, and stemness in a ROS-dependent manner. RNA sequencing results confirm that SMFs increased the oxidative stress level and reduced the stemness of ovarian cancer cells. Consistently, the expressions of stemness-related genes were significantly decreased, including hyaluronan receptor (CD44), SRY-box transcription factor 2 (Sox2), and cell myc proto-oncogene protein (C-myc). Furthermore, moderate SMFs provided by a superconducting magnet and permanent magnet have good biosafety and can both inhibit ovarian cancer metastasis in mice. Therefore, our study demonstrates the effects of SMFs on oxidative stress and metastasis in the ovarian cancer cells, which reveals the potential of applying SMF as a physical method in cancer therapy in the future.

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Wnt5A modulates integrin expression in a receptor-dependent manner in ovarian cancer cells

Scientific Reports ◽

10.1038/s41598-021-85356-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Vajihe Azimian-Zavareh ◽

Zeinab Dehghani-Ghobadi ◽

Marzieh Ebrahimi ◽

Kian Mirzazadeh ◽

Irina Nazarenko ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cell Attachment ◽

Ovarian Cancer Cells ◽

Integrin Expression ◽

Dependent Manner ◽

Cancer Cell Proliferation ◽

Expression Levels ◽

Multicellular Aggregates ◽

Focal Adhesion Kinase Activity

AbstractWnt5A signals through various receptors that confer versatile biological functions. Here, we used Wnt5A overexpressing human ovarian SKOV-3 and OVCAR-3 stable clones for assessing integrin expression, cell proliferation, migration, invasion, and the ability of multicellular aggregates (MCAs) formation. We found here, that Wnt5A regulates differently the expression of its receptors in the stable Wnt5A overexpressing clones. The expression levels of Frizzled (FZD)-2 and -5, were increased in different clones. However ROR-1, -2 expression levels were differently regulated in clones. Wnt5A overexpressing clones showed increased cell proliferation, migration, and clonogenicity. Moreover, Wnt5A overexpressing SKOV-3 clone showed increased MCAs formation ability. Cell invasion had been increased in OVCAR-3-derived clones, while this was decreased in SKOV-3-derived clone. Importantly, αv integrin expression levels were increased in all assessed clones, accompanied by increased cell attachment to fibronectin and focal adhesion kinase activity. Moreover, the treatment of clones with Box5 as a Wnt5A/FZD5 antagonist abrogates ITGAV increase, cell proliferation, migration, and their attachment to fibronectin. Accordingly, we observed significantly higher expression levels of ITGAV and ITGB3 in human high-grade serous ovarian cancer specimens and ITGAV correlated positively with Wnt5A in metastatic serous type ovarian cancer. In summary, we hypothesize here, that Wnt5A/FZD-5 signaling modulate αv integrin expression levels that could be associated with ovarian cancer cell proliferation, migration, and fibronectin attachment.

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Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02274-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Qingjuan Meng ◽

Ningning Wang ◽

Guanglan Duan

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Invasion And Migration ◽

Non Coding Rna ◽

And Migration ◽

Long Non Coding Rna

Abstract Background X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. Methods RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. Results The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. Conclusion XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.

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FBXO6-mediated RNASET2 ubiquitination and degradation governs the development of ovarian cancer

Cell Death and Disease ◽

10.1038/s41419-021-03580-4 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Mei Ji ◽

Zhao Zhao ◽

Yue Li ◽

Penglin Xu ◽

Jia Shi ◽

...

Keyword(s):

Ovarian Cancer ◽

Inverse Correlation ◽

Degradation Pathway ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Poor Overall Survival ◽

Protein Levels ◽

Ubiquitin E3 Ligase ◽

Ovarian Tumorigenesis ◽

F Box Protein

AbstractRNASET2 (Ribonuclease T2) functions as a tumor suppressor in preventing ovarian tumorigenesis. However, the mechanisms underlying the regulation of RNASET2 protein are completely unknown. Here we identified the F-box protein FBXO6, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the ubiquitin E3 ligase for RNASET2. We found that the interaction between FBXO6 and RNASET2 induced RNASET2 instability through the ubiquitin-mediated proteasome degradation pathway. FBXO6 promoted K48-dependent ubiquitination of RNASET2 via its FBA domain. Through analysis of the TCGA dataset, we found that FBXO6 was significantly increased in ovarian cancer tissues and the high expression of FBXO6 was related to the poor overall survival (OS) of ovarian cancer patients at advanced stages. An inverse correlation between the protein levels of FBXO6 and RNASET2 was observed in clinic ovarian cancer samples. Depletion of FBXO6 promoted ovarian cancer cells proliferation, migration, and invasion, which could be partially reversed by RNASET2 silencing. Thus, our data revealed a novel FBXO6-RNASET2 axis, which might contribute to the development of ovarian cancer. We propose that inhibition of FBXO6 might represent an effective therapeutic strategy for ovarian cancer treatment.

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