Sevoflurane but not propofol enhances ovarian cancer cell malignancy through regulating cellular metabolic and signalling mechanisms

Background and Purpose: Surgery remains the first-line treatment of ovarian cancer. However, perioperative risk factors including the choice of anaesthetics may influence its recurrence after surgery. In the current study, it was hypothesised that inhalational anaesthetic sevoflurane and intravenous anaesthetic propofol might affect cancer cellular metabolism and signalling, which might interfere the malignancy of ovarian cancer cells. Experimental Approach: Cultured ovarian cancer cells were exposed to 2.5% sevoflurane or administered with 4 μg/mL propofol for 2 hours followed by 24 hours recovery. Their cell viability, proliferation, migration and invasion were assessed using cell counting kit-8, Ki-67 staining, wound healing and Transwell assay. Cellular signalling biomarkers were measured using immunofluorescent staining and/or Western blot. Cultured media were collected for 1H-NMR spectroscopy-based metabolomics analysis. Key Results: The cell viability, proliferation, migration, and invasion of ovarian cancer cells were enhanced by sevoflurane but suppressed by propofol. Sevoflurane increased the GLUT1, MPC1, GLUD1, p-Erk1/2, and HIF-1α expressions but decreased the PEDF expression. In contrast to the sevoflurane treatment, the “mirror changes” of these cellular markers were observed with propofol. Sevoflurane increased levels of isopropanol but decreased glucose and glutamine levels in the media, but the opposite changes of those metabolites were found after propofol treatment. Conclusion and Implications: These data indicated that unlike propofol, sevoflurane enhanced ovarian cancer cell metabolism and activated PEDF/Erk/HIF-1α cellular signalling pathway, suggesting that sevoflurane might have pro-tumour property but propofol might afford an anti-tumour property. The translational value of this work warrants further study.

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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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ID: 45: EVALUATION OF CELLULAR MECHANISMS BY WHICH CINOBUFOTALIN INHIBITS OVARIAN CANCER CELL LINES FUNCTION

Journal of Investigative Medicine ◽

10.1136/jim-2016-000120.77 ◽

2016 ◽

Vol 64 (4) ◽

pp. 950.1-950 ◽

Cited By ~ 1

Author(s):

SH Afroze ◽

DC Zawieja ◽

R Tobin ◽

C Peddaboina ◽

MK Newell-Rogers ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Ovarian Cancer Cells ◽

Ovarian Cancer Cell Lines

ObjectiveCinobufotalin (CINO), a cardiotonic steroid (CTS) or bufadienolide, is extracted from the skin secretions of the traditional Chinese medicine giant toads (Chan su). CINO has been used as a cardiotonic, diuretic and a hemostatic agent. Previously we have shown that CINO inhibits the cytotrophoblast cell function. Recently other study has shown that CINO inhibits A549, a lung cancer cell function. In this study, we assessed the effect of CINO on three different ovarian cancer cell lines; SK-OV-3, CRL-1978 and CRL-11731 to confirm whether the effect of CINO is cell specific.Study DesignWe evaluated the effect of CINO on three ovarian cancer cells SK-OV-3, CRL-1978, and CRL-11731 function in vitro. Each Cell lines were treated with different concentrations of CINO (0.1, 1, 5 and 10 µM). For each cell line cell proliferation, migration and invasion were measured by using a CellTiter Assay (Promega), Cytoselect Assay (Cell Biolabs) and by using a FluoroBlock Assay (BD) respectively. Proliferating Cell Nuclear Antigen (PCNA) was also evaluated in cell lysates of CINO treated these 3 ovarian cancer cells by western blot analysis. Cell Cycle arrest and Cell viability were determined by fluorescence-activated cell sorting (FACS) analysis. We also performed Annexin V staining on CINO treated these 3 ovarian cancer cell lines by immunofluorescence to evaluate the pro-apoptotic protein expression. In addition mitochondrial membrane potential has also been measured for all these 3 ovarian cell lines after CINO treatment using MMP kit, by FACS analysis.ResultsConcentration of CINO at 0.5 µM inhibit SK-OV-3, CRL-1978, and CRL-11731 ovarian cancer cells proliferation, migration and invasion without cell death and loss of cell viability but cell viability differs for each cell line. Each cell lines differ in response to CINO doses for PCNA expression as well as Annexin V pro-apoptotic protein expression. CINO decreases mitochondrial membrane potential for SK-OV-3 but for CRL-1978 and CRL-11731 increases in response to CINO treatment.ConclusionCINO is cell specific, as each cancer cell line responds differently. These data demonstrate that the mode of action of CINO is different on these 3 types of ovarian cancer cells.

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CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate

Cancers ◽

10.3390/cancers12082269 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2269

Author(s):

Aalia Batool ◽

Hao Liu ◽

Yi-Xun Liu ◽

Su-Ren Chen

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Mapk Signaling ◽

Migration And Invasion ◽

Integrated Analysis ◽

Ovarian Cancer Cells ◽

Spheroid Formation ◽

Regulation Of Proliferation

Ovarian cancer is a leading cause of death from gynecologic malignancies worldwide. Although CD83 is widely described as a solid marker for mature dendritic cells, emerging pieces of evidence indicate the expression of membrane protein CD83 by various tumor cells, including ovarian cancer cells. However, the potential role of CD83 in ovarian cancer cell properties and development remains absolutely unknown. By using human CD83 stable overexpression and knockdown sublines of several ovarian cancer cells, we observed that CD83 advanced the growth proliferation, colony formation ability, spheroid formation, and in vivo tumorigenicity of ovarian cancer cells; surprisingly, CD83 limited their migration and invasion potentials. Positive regulation of proliferation/stemness factors (e.g., cyclin-CDKs and KIT/CD44) but negative regulation of matrix metallopeptidases (e.g., MMP1 and 7) by CD83 were revealed by the integrated analysis of transcriptome and proteome. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) first identified the association of CD83 with MAP3K7 (also known as TAK1) and MAP3K7-binding protein TAB1 on the cell membrane. Moreover, CD83 functions through the activation of MAP3K7-MEK1/2-ERK1/2 cascades to further regulate downstream FOXO1/p21/CDK2/CCNB1 and STAT3/DKK1 signaling pathways, thus activating proliferation and spheroid formation of ovarian cancer cells, respectively. Collectively, our findings define a CD83-MAPK pathway in the regulation of proliferation and stemness in ovarian cancer cells, with potential therapeutic applications in blocking their progression.

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Dezocine inhibits cell proliferation, migration and invasion by targeting CRABP2 in ovarian cancer

10.21203/rs.3.rs-16025/v1 ◽

2020 ◽

Author(s):

Chuanfeng Zhang ◽

Ruirui Pan ◽

Shuangshuang Ma ◽

Shoucai Xu ◽

Baosheng Wang

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Metastatic Potential ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Mechanism Study ◽

Skov3 Cells

Abstract Background Previous studies have shown that some anesthesia drugs can inhibit tumor growth and metastasis. As a clinical anesthetic drug, dezocine has been reported to play an important role in immune function. However, the effects of dezocine on ovarian cancer cell growth and metastasis are not fully understood. Results In this study, we found that dezocine dose-dependently inhibited the viability of ES-2 and SKOV3 cells. Dezocine suppressed the migration and invasion abilities of ovarian cancer cells, and promoted apoptosis. Moreover, the Akt/mTOR signaling pathway was also inhibited by dezocine. Furthermore, mechanism study showed that dezocine could significantly inhibited the expression of CRABP2, and CRABP2 overexpression reversed the inhibitory effects of dezocine on ovarian cancer cell proliferation and migration. Conclusion In conclusion, dezocine has significant anti-tumor effects on the growth and metastatic potential of ovarian cancer cells, and CRABP2 functions as a downstream effector of dezocine.

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Sevoflurane and Desflurane Exposure Enhanced Cell Proliferation and Migration in Ovarian Cancer Cells via miR-210 and miR-138 Downregulation

International Journal of Molecular Sciences ◽

10.3390/ijms22041826 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1826 ◽

Cited By ~ 1

Author(s):

Masashi Ishikawa ◽

Masae Iwasaki ◽

Hailin Zhao ◽

Junichi Saito ◽

Cong Hu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cell Counting ◽

Immunofluorescent Staining ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

Inhalational anaesthetics were previously reported to promote ovarian cancer malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the role of sevoflurane- or desflurane-induced microRNA (miRNA) changes on ovarian cancer cell behaviour. The cultured SKOV3 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. Expression of miR-138, -210 and -335 was determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and Cell Counting Kit-8 (CCK8) assay with or without mimic miR-138/-210 transfections. The miRNA downstream effector, hypoxia inducible factor-1α (HIF-1α), was also analysed with immunofluorescent staining. Sevoflurane or desflurane exposure to cancer cells enhanced their proliferation and migration. miR-138 expression was suppressed by both sevoflurane and desflurane, while miR-210 expression was suppressed only by sevoflurane. miR-335 expression was not changed by either sevoflurane or desflurane exposure. The administration of mimic miR-138 or -210 reduced the promoting effects of sevoflurane and desflurane on cancer cell proliferation and migration, in line with the HIF-1α expression changes. These data indicated that inhalational agents sevoflurane and desflurane enhanced ovarian cancer cell malignancy via miRNA deactivation and HIF-1α. The translational value of this work needs further study.

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Effect of valproic acid on cisplatin-resistant ovarian cancer cell lines

Journal of Shahrekord University of Medical Sciences ◽

10.34172/jsums.2019.07 ◽

2019 ◽

Vol 21 (1) ◽

pp. 39-44

Author(s):

Somayeh Hashemi-Sheikhshabani ◽

Zeinab Amini-Farsani ◽

Mehdi Shamsara ◽

Zahra Sajadpoor ◽

Mohammad Hossein Sangtarash ◽

...

Keyword(s):

Ovarian Cancer ◽

Valproic Acid ◽

Cell Viability ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Ovarian Cancer Cells ◽

Platinum Resistance ◽

Ovarian Cancer Cell Lines

Background and aims: Platinum resistance has been one of the most important problems in the management of ovarian cancer. The effects of various chemotherapeutic agents are limited in patients with platinum resistance. Therefore, developing new anticancer drugs that can improve the effect of currently used cytostatics is critical. The current study investigated the effects of valproic acid (VPA) alone and in combination with cisplatin on ovarian cancer cells. Methods: In this experimental study, the human ovarian cancer cell lines (A2780-S and A2780-CP) were grown in RPMI-1640 medium in appropriate culture conditions. The cells were treated with various concentrations of cisplatin (0.15-400 µg/mL) or VPA (10-2000 µg/mL) and were incubated for 24, 48, and 72 hours. Moreover, A2780 cells were co-treated with different concentrations of cisplatin and VPA for 48 hours. Afterward, cell viability was investigated using MTT assay. GraphPad Prism statistical software was used for the data analysis and ANOVA and Duncan’s test were conducted. Results: A dose- and time-dependent reduction was observed in cell viability following the treatment with cisplatin or VPA. Moreover, cotreatment of the A2780 cells with cisplatin and VPA resulted in a significantly greater inhibition of cell viability compared to the treatment with either agent alone. Conclusion: Overall, it can be argued that VPA does not only cause inhibition of proliferation and induction of apoptosis in ovarian cancer cells but also helps to enhance the antiproliferative effects of cisplatin and results in the increased susceptibility to cisplatin in resistant cells. VPA may therefore be used to treat cancer in the future.

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Dezocine inhibits cell proliferation, migration and invasion by targeting CRABP2 in ovarian cancer

10.21203/rs.3.rs-16025/v2 ◽

2020 ◽

Author(s):

Chuanfeng Zhang ◽

Ruirui Pan ◽

Shuangshuang Ma ◽

Shoucai Xu ◽

Baosheng Wang

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Metastatic Potential ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Mechanism Study ◽

Skov3 Cells

Abstract Background: Previous studies have shown that some anesthesia drugs can inhibit tumor growth and metastasis. As a clinical anesthetic drug, dezocine has been reported to play an important role in immune function. However, the effects of dezocine on ovarian cancer cell growth and metastasis are not fully understood. Results: In this study, we found that dezocine dose-dependently inhibited the viability of ovarian cancer ES-2 and SKOV3 cells. Dezocine suppressed the migration and invasion abilities of ovarian cancer cells and promoted apoptosis. Moreover, the Akt/mTOR signaling pathway was also inhibited by dezocine. Furthermore, the mechanism study showed that dezocine could significantly inhibit the expression of CRABP2, and CRABP2 overexpression reversed the inhibitory effects of dezocine on ovarian cancer cell proliferation and migration. Conclusions: In conclusion, dezocine has significant anti-tumor effects on the growth and metastatic potential of ovarian cancer cells, and CRABP2 functions as a downstream effector of dezocine.

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CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion

Cancers ◽

10.3390/cancers13112745 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2745

Author(s):

Miran Jeong ◽

Yi-Yue Wang ◽

Ju-Yeon Choi ◽

Myong-Cheol Lim ◽

Jung-Hye Choi

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Invasion ◽

Ovarian Cancer Cell ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Cancer Cell Invasion ◽

Cc Chemokine ◽

Chemokine Ligand

In the tumor microenvironment, macrophages have been suggested to be stimulated by tumor cells, becoming tumor-associated macrophages that promote cancer development and progression. We examined the effect of these macrophages on human ovarian cancer cell invasion and found that conditioned medium of macrophages stimulated by ovarian cancer cells (OC-MQs) significantly increased cell invasion. CC chemokine ligand 7 (CCL7) expression and production were significantly higher in OC-MQs than in the control macrophages. Peritoneal macrophages from patients with ovarian cancer showed higher CCL7 expression levels than those from healthy controls. Inhibition of CCL7 using siRNA and neutralizing antibodies reduced the OC-MQ-CM-induced ovarian cancer cell invasion. CC chemokine receptor 3 (CCR3) was highly expressed in human ovarian cancer cells, and a specific inhibitor of this receptor reduced the OC-MQ-CM-induced invasion. Specific signaling and transcription factors were associated with enhanced CCL7 expression in OC-MQs. CCL7-induced invasion required the expression of matrix metalloproteinase 9 via activation of extracellular signal-related kinase signaling in human ovarian cancer cells. These data suggest that tumor-associated macrophages can affect human ovarian cancer metastasis via the CCL7/CCR3 axis.

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LncRNA SDHAP1 confers paclitaxel resistance of ovarian cancer by regulating EIF4G2 expression via miR-4465

The Journal of Biochemistry ◽

10.1093/jb/mvaa036 ◽

2020 ◽

Vol 168 (2) ◽

pp. 171-181 ◽

Cited By ~ 7

Author(s):

Hui Zhao ◽

Aixia Wang ◽

Zhiwei Zhang

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Regulatory Function ◽

Ovarian Cancer Cells ◽

Chemotherapeutic Resistance ◽

Ovarian Cancer Cell Lines

Abstract Ovarian cancer has ranked as one of the leading causes of female morbidity and mortality around the world, which affects ∼239,000 patients and causes 152,000 deaths every year. Chemotherapeutic resistance of ovarian cancer remains a devastating actuality in clinic. The aberrant upregulation of long non-coding RNA succinate dehydrogenase complex flavoprotein subunit A pseudogene 1 (lncRNA SDHAP1) in the Paclitaxel (PTX)-resistant ovarian cancer cell lines has been reported. However, studies focussed on SDHAP1 in its regulatory function of chemotherapeutic resistance in ovarian cancer are limited, and the detailed mechanisms remain unclear. In this study, we demonstrated that SDHAP1 was upregulated in PTX-resistant SKOV3 and Hey-8 ovarian cancer cell lines while the level of miR-4465 was downregulated. Knocking-down SDHAP1 induced re-acquirement of chemo-sensitivity to PTX in ovarian cancer cells in vitro. Mechanically, SDHAP1 upregulated the expression of EIF4G2 by sponging miR-4465 and thus facilitated the PTX-induced apoptosis in ovarian cancer cells. The regulation network involving SDHAP1, miR-4465 and EIF4G2 could be a potential therapy target for the PTX-resistant ovarian cancer.

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