scholarly journals MicroRNA-101 inhibits growth and metastasis of human ovarian cancer cells by targeting PI3K/AKT

2021 ◽  
Vol 17 (1) ◽  
pp. 127-134
Author(s):  
Min Wei ◽  
Hongjuan Jin ◽  
ShuLi Yang ◽  
Zhuo Li ◽  
Xinlei Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Pten Expression ◽  
Cell Cycle Analysis ◽  
Ovarian Cancer Cells ◽  
G1 Arrest ◽  
Down Regulation ◽  
Over Expression

IntroductionOvarian cancer is the most frequent cause of gynecological cancer related mortality in woman. This study was designed to investigate the role and therapeutic potential of miRNA-101 in ovarian cancer.Material and methodsExpression analysis was carried out by real-time quantitative polymerase chain reaction. Transfections were performed with the help of Lipofectamine 2000 reagent. AO/EB and annexin V/PI staining was used to detect apoptosis and flow cytometry was used for cell cycle analysis. Western blotting was employed for cell cycle analysis.ResultsIt was found that miRNA-101 was significantly down-regulated in ovarian cancer cells. The over-expression of miRNA-101 causes a significant decrease in the viability of ovarian cancer cells via the initiation of apoptosis and sub-G1 arrest of OVACAR-3 cells. It was indicated that PTEN was the potential target of miRNA-101 in OVACAR-3 cells. There was 4.5-fold up-regulation of PTEN expression in ovarian cancer cell lines and the over-expression of miRNA-101 in OVACAR-3 cells resulted in the down-regulation of PTEN expression. The inhibition of PTEN in the OVACAR-3 cells arrested the proliferation of these cells. The over-expression of miRNA-101 causes significant down-regulation in PI3K and AKT expression of OVACAR-3 cells.ConclusionsIt can be concluded that miRNA-101 acts as a tumor suppressor which may be beneficial in the treatment of ovarian cancer.

scholarly journals ATM Regulated PTEN Degradation Is XIAP E3 Ubiquitin Ligase Mediated in p85α Deficient Cancer Cells and Influence Platinum Sensitivity

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1271 ◽  
Author(s):  
Reem Ali ◽  
Muslim Alabdullah ◽  
Islam Miligy ◽  
Makhliyo Normatova ◽  
Roya Babaei-Jadidi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Progression Free Survival ◽  
Strand Break ◽  
Pten Expression ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Platinum Sensitivity ◽  
Apoptosis Protein

Ataxia-telegiectasia mutated (ATM), phosphatase and tensin homolog (PTEN), and p85α are key tumour suppressors. Whether ATM regulates PTEN expression and influence platinum sensitivity is unknown. We generated ATM knockdowns (KD) and CRISPR knock outs (KO) in glioblastoma (LN18, LN229) and ovarian cancer cells (OVCAR3, OVCAR4). Doxycycline inducible PTEN expression was generated in LN18 and LN229 cells. Transient KD of p85α, CK2, and XIAP was accomplished using siRNAs. Stable p85α knock-in was isolated in LN18 cells. Molecular biology assays included proteasome activity assays, PCR, flow cytometry analysis (cell cycle, double strand break accumulation, apoptosis), immunofluorescence, co-immunoprecipitation, clonogenic, invasion, migration, and 3D neurosphere assays. The clinicopathological significance of ATM, PTEN, p85α, and XIAP (X-linked inhibitor of apoptosis protein) was evaluated in 525 human ovarian cancers using immunohistochemistry. ATM regulated PTEN is p85α dependant. ATM also controls CK2α level which in turn phosphorylates and stabilizes PTEN. In addition, p85α physically interacts with CK2α and protects CK2α from ATM regulated degradation. ATM deficiency resulted in accumulation of XIAP/p-XIAP levels which ubiquitinated PTEN and CK2α thereby directing them to degradation. ATM depletion in the context of p85α deficiency impaired cancer cell migration and invasion reduced 3D-neurosphere formation and increased toxicity to cisplatin chemotherapy. Increased sensitivity to platinum was associated with DNA double strand breaks accumulation, cell cycle arrest, and induction of autophagy. In ovarian cancer patients, ATM, PTEN, p85α, and XIAP protein levels predicted better progression free survival after platinum therapy. We unravel a previously unknown function of ATM in the regulation of PTEN throμgh XIAP mediated proteasome degradation.

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.

Adenosine Analogues as Opposite Modulators of the Cisplatin Resistance of Ovarian Cancer Cells

2019 ◽  
Vol 19 (4) ◽  
pp. 473-486 ◽  
Author(s):  
Katarzyna Bednarska-Szczepaniak ◽  
Damian Krzyżanowski ◽  
Magdalena Klink ◽  
Marek Nowak
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Biology ◽  
Immune Cell ◽  
Immunosuppressive Agents ◽  
Cell Activity ◽  
Ovarian Cancer Cells ◽  
Adenosine Analogues

Background: Adenosine released by cancer cells in high amounts in the tumour microenvironment is one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive and cisplatin-resistant ovarian cancer cells to cisplatin treatment. Methods: The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/ antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis events and cisplatin incorporation in cancer cells were determined. Results: PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring mitochondrial and plasma membrane potentials that were disturbed by cisplatin. Conclusion: Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell biology should be considered in the context of supportive chemotherapy for ovarian cancer.

scholarly journals 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

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.

scholarly journals The BRCA2 p.N372 H i.a.1342A>C Could Regulate the Sensitivity of Ovarian Cancer Cells to Platinum-Based Drugs

2020 ◽  
Vol 19 ◽  
pp. 153303382098328
Author(s):  
Zhen-Hua Du ◽  
Yu Xia ◽  
Qing Yang ◽  
Song Gao
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Mutant Gene ◽  
Negative Control ◽  
Ovarian Cancer Cells ◽  
Platinum Resistance ◽  
Over Expression ◽  
Ic50 Value ◽  
Brca2 Protein ◽  
Recombination Repair

Background and Objective: We have previously reported that BRCA2 N372 H i.a.1342A>C heterozygous variation presented in platinum-resistant patients. This study aimed to further investigate the mechanism of BRCA2 N372 H mutation in the development of platinum resistance in ovarian cancer. Methods: The BRCA2 N372 H i.a.1342A>C was synthesized and used to exchange 1 wildtype allele followed by sequencing to confirm the mutant allele sequence. Plasmids were constructed and transfected into the OVCAR-3 cells after lentiviral packaging. BRCA2 N372 H mRNA was detected by qPCR. BRCA2 protein was assessed by immunoblotting. Binding of the BRCA2 to Rad51 was detected by immunofluorescence staining. Sensitivity of the cells to cisplatin treatment was assessed with CCK-8 assay. Results: It was found that expression of BRCA2 protein in ovarian cancer cells transfected with BRCA2 N372 H i.a.1342A>C gene (2.177 ± 0.003) was significantly increased compared to that of the cells transfected with lenti-EGFP only (1.227 ± 0.003, P < 0.001). Binding of the BRCA2 and Rad51 proteins was significantly increased in the cells with BRCA2 N372 H i.a.1342A>C mutation (3.542 ± 0.24) than that in the cells transfected with lenti-EGFP (1.29 ± 0.32) or empty cells (1.363 ± 0.32, P < 0.001). Cell viability significantly increased in the cells transfected with BRCA2 N372 H mutant gene. The IC50 value was significantly higher in the cells transfected with BRCA2 N372 H mutant gene (1.963 ± 0.04) than that of the cells transfected with lenti-EGFP (0.955 ± 0.03, P < 0.01) or empty cells (1.043 ± 0.007, P < 0.01). Conclusion: Over expression of mRNA and protein of BRCA2 was detected in the cells with BRCA2 N372 H i.a.1342A>C mutation but not in the lentivirus negative control (lenti-EGFP) or the cells without transfection (empty cells), which may lead to resistance to platinum-based drugs in ovarian cancer cells through homologous recombination repair pathway.

scholarly journals Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

2010 ◽  
Vol 9 (1) ◽  
pp. 47 ◽  
Author(s):  
Christopher S Bryant ◽  
Sanjeev Kumar ◽  
Sreedhar Chamala ◽  
Jay Shah ◽  
Jagannath Pal ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest

scholarly journals 5, 7-Dihalo-8-quinolinol complex inhibits growth of ovarian cancer cells via the downregulation of expression of Wip1

2020 ◽  
Vol 19 (7) ◽  
pp. 1417-1422
Author(s):  
Rao Zhiwei ◽  
Xia Songbai ◽  
Han Qi
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cytotoxic Effect ◽  
Ovarian Cancer Cell ◽  
Drug Candidate ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Growth ◽  
Protein Expressions ◽  
G0 Phase

Purpose: To assess the cytotoxic effect of 5, 7-dihalo-8-quinolinol complex (DHQ) on ovarian cancer cells, and the mechanism of action involved.Methods: DHQ-mediated changes in cell viability were determined using MTT assay, while apoptosis was analyzed with flow cytometry. The effect of DHQ on cell migration was determined using inverted microscopy, while its effect on invasiveness was assessed with Giemsa dyeing. FACS Caliburinstrumentation was employed for analyzing the effect of DHQ on the cell cycle. The protein expressions of Wip1 and P53 were assayed by western blotting.Results: DHQ induced cytotoxicity against A2780 and OVCAR 3 cells in the concentration range of 0.25 - 12 μM (p < 0.05). In A2780 and OVCAR 3 cells, treatment with 12 μMDHQ resulted in 69.34 and 65.46 % apoptosis, respectively. The migratory potential and invasiveness of A2780 and OVCAR3 cells were significantly decreased by 12 μMDHQ, relative to untreated cells (p < 0.05). Moreover, treatment with 12 μMDHQ arrested cell cycle at G1/G0 phase in A2780 and OVCAR3 cells, but downregulated the protein expressions of Wip1 expression in A2780 and OVCAR3 cells.Conclusion: DHQ exerts cytotoxic effect on ovarian cancer cell growth via arrest of cell cycle and activation of apoptosis. Moreover, DHQ inhibits the migratory and invasive abilities of the cells. Thus, DHQ is a potential drug candidate for the management of ovarian cancer. Keywords: 5,7-Dihalo-8-quinolinol complex, Ovarian cancer, Cytotoxicity, Apoptosis, Invasiveness, Migration, Cell cycle

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