• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6429-6433
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• 2012

To explore a possible new treatment for human ovarian cancer, we studied the effects of sodium valproate on the growth of the HO8910 human cell line. HO8910 cells were cultured in vitro and treated with different concentrations of sodium valproate. Cell proliferation, cell cycling, and apoptosis were measured by flow cytometry, cell morphology under a microscope, and expression levels of WWOX and P27 by Western blotting and RT-PCR. Tumor xenografts were established to determine in vivo effects of sodium valproate. Our results showed that cell proliferation was decreased with increasing concentration of sodium valproate, with features of cytoplasmic retraction and floating cells. Moreover, cell cycle analysis revealed a higher apoptosis rate and $G_0/G_1$ phase in the sodium valproate experimental group than in the control group. In addition, protein expression levels of WWOX and P27 were elevated. Importantly, sodium valproate decreased in vivo xenograft tumor burden and up-regulated WWOX and P27 expression in nude mice. In conclusion, sodium valproate might play a role in inhibition and control of ovarian cancer cell line HO8910 by inhibiting cell proliferation, interfering with the cell cycle and promoting apoptosis, so that it may be effective in the clinical treatment of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3573-3577
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• 2015

Background: Sirtuin7 (SIRT7) is a type of nicotinamide adenine dinucleotide oxidized form (NAD+)-dependent deacetylase and the least understood member of the sirtuins family; it is implicated in various processes, such as aging, DNA damage repair and cell signaling transduction. There is some evidence that SIRT7 may function as a tumor trigger for human malignancy. Here, we aimed to explore the biological function of SIRT7 in ovarian carcinoma cells and its potential mechanism. Materials and Methods: Expression of SIRT7 in ovarian cancer cell lines was detected by western blotting. Transduced cell lines with SIRT7 knockdown or overexpression were constructed. Cell viability, cologenic, apoptosis-associated and motility assays were performed to elucidate the biological function of SIRT7 in ovarian cancer cells. Results: SIRT7 demonstrated a higher level in ovarian cancer cell lines compared with normal cells. On the one hand, down-regulation of SIRT7 significantly reduced ovarian cancer cell growth, repressed colony formation and increased cancer cell apoptosis; on the other hand, up-regulation promoted the migration of cancer cells. Additionally, repression of SIRT7 also induced change in apoptosis-related molecules and subunits of the NF-${\kappa}B$ family. Conclusions: In the present study, our data indicated that SIRT7 might play a role of oncogene in ovarian malignancy and be a potential therapeutic target.

• BMB Reports
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• v.40 no.2
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• pp.290-294
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• 2007

Saxatilin is a disintegrin known to inhibit tumor progression in vivo and in vitro. The role of saxatilin in cancer cell invasion was examined by a modified Boyden chamber assay in MDAH 2774 human ovarian cancer cell line. Saxatilin (50 nM) significantly inhibited cancer cell invasion induced by tumor necrosis factor-$\alpha$ (TNF-a$\alpha$). Saxatilin also reduced MMP-9 mRNA levels in cancer cells in a dosedependent manner. In addition, TNF-$\alpha$-induced MMP-9 activity was reduced by the treatment of saxatilin. These results indicate that transcriptional regulation of MMP-9 is an important mechanism for the tumor suppressive effects of saxatilin in MDAH 2774 human ovarian cancer cells.

• Reproductive and Developmental Biology
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• v.37 no.1
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• pp.41-49
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• 2013

Ovarian cancer is the most lethal world-wide gynecological disease among women due to the lack of molecular biomarkers to diagnose the disease at an early stage. In addition, there are few well established relevant animal models for research on human ovarian cancer. For instance, rodent models have been established through highly specialized genetic manipulations, but they are not an excellent model for human ovarian cancer because histological features are not comparable to those of women, mice have a low incidence of tumorigenesis, and they experience a protracted period of tumor development. However, the laying hen is a unique and highly relevant animal model for research on human ovarian cancer because they spontaneously develop epithelial cell-derived ovarian cancer (EOC) as occurs in women. Our research group has identified common histological and physiological aspects of ovarian tumors from women and laying hens, and we have provided evidence for several potential biomarkers to detect, monitor and target for treatment of human ovarian cancers based on the use of both genetic and epigenetic factors. Therefore, this review focuses on ovarian cancer of laying hens and relevant regulatory mechanisms, based on genetic and epigenetic aspects of the disease in order to provide new information and to highlight the advantages of the laying hen model for research in ovarian carcinogenesis.

• Animal cells and systems
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• v.1 no.2
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• pp.389-394
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• 1997

We examined the effect of modulation of PKA isozymes on the growth of human ovarian cancer cells. Three ovarian cancer cell lines, 2774, SK-OV-3, and OVCAR-3, were examined in this study. The treatment of 5 uM 8-CI-cAMP, which has been known to down-regulate RI (or type 1 PKA) and up-regulate RII (or type II PKA), markedly inhibited the growth of all cell lines (50-80% at day 6). To test whether alteration in PKA regulatory subunits level can change the growth characteristics of ovarian cancer cells, we introduced RIIB- expression construct and Rla antisense-expression construct into 2774 cells. The overexpression of RIIB down-regulated Rla protein, and the antisense-expression of Rla up-regulated RIIB protein, showing that the intracellular levels of RI and RII are reciprocally regulated. In both cases, cell growth was reduced by 30% at day 2. These results indicate that the growth of ovarian cancer cells is controlled by the signals from PKA isozymes, and the modulation of PKA isozymes can be employed for the human ovarian cancer therapy.

• International Journal of Oncology
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• v.56 no.2
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• pp.618-629
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• 2020

Bcl2l10, also known as Diva, Bcl-b and Boo, is a member of the Bcl2 family of proteins, which are involved in signaling pathways that regulate cell apoptosis and autophagy. Previously, it was demonstrated that Bcl2l10 plays a crucial role in the completion of oocyte meiosis and is a key regulator of Aurora kinase A (Aurka) expression and activity in oocytes. Aurka is overexpressed in several types of solid tumors and has been considered a target of cancer therapy. Based on these previous results, in the present study, the authors aimed to investigate the regulatory role of Bcl2l10 in A2780 and SKOV3 human ovarian cancer cells. The protein expression of Bcl2l10 was examined in human cancer tissues and cell lines, including the ovaries, using a tissue microarray and various human ovarian cancer cell lines. It was found that Bcl2l10 regulated the protein stability and activities of Aurka in ovarian cancer cells. Although apoptosis was not affected, the cell cycle was arrested at the G0/G1 phase by Bcl2l10 knockdown. Of note, cell viability and motility were markedly increased by Bcl2l10 knockdown. On the whole, the findings of this study suggest that Bcl2l10 functions as tumor suppressor gene in ovarian cancer.

• BMB Reports
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• v.43 no.8
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• pp.554-560
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• 2010

Smad4 is involved in cancer progression and metastasis. Using a pair of human syngeneic epithelial ovarian cancer cells with low (HO-8910) and high (HO-8910PM) metastatic abilities, we aimed to reveal the role of Smad4 in ovarian cancer metastasis in vitro. Smad4 was down-regulated in HO-8910PM cell line relative to HO-8910 by implicating Smad4 was probably a potential tumor suppressor gene for ovarian cancer. Re-expression of Smad4 decreased the migration ability and inhibited the invasion capacity of HO-8910PM, while promoted the cell adhesion capacity for HO-8910PM. The stable expression of Smad4 increased the expression of E-cadherin, reduced the expression of plasminogen activator inhibitor-1 (PAI-1) and slightly down-regulated the expression of VEGF. Smad4 suppresses human ovarian cancer cell metastasis potential through its effect on the expressions of PAI-1, E-cadherin and VEGF. Results from current work implicate Smad4 might suppress the invasion and metastasis of human ovarian tumor cells through a TGF-$\beta$/Smad-mediated pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1343-1348
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• 2015

Human UHRF1 (ubiquitin-like PHD and RING finger domain-containing 1) has been reported to be over-expressed in many cancers, but its role in ovarian cancer remains elusive. Here, we determined whether knockdown of UHRF1 by lentivirus-mediated shRNA could inhibit ovarian cancer cell growth. Lentivirus-mediated short hairpin RNAs (lv-shRNAs-UHRF1) were designed to trigger the gene silencing RNA interference (RNAi) pathway. The efficiency of lentivirus-mediated shRNA infection into HO-8910 and HO-8910 PM cells was determined using fluorescence microscopy to observe lentivirus-mediated GFP expression and was confirmed to be over 80 percent. UHRF1 expression in infected HO-8910 and HO-8910 PM was evaluated by real-time PCR and Western blot analysis. The Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability; flow cytometry and Hoechst 33342 assay was applied to measure cell cycle arrest and apoptosis. Cell invasion was assessed using transwell chambers. Our results demonstrated that the loss of UHRF1 promoted HO-8910 and HO-8910 PM cell apoptosis, while inhibiting cell proliferation. In addition, UHRF1 knockdown significantly inhibited the invasion of human ovarian cancer cells. In the present study, we also showed that depleting HO-8910 cells of UHRF1 caused activation of the DNA damage response pathway, with the cell cycle arrested in G2/M-phase. The DNA damage response in cells depleted of UHRF1 was illustrated by phosphorylation of CHK (checkpoint kinase) 2 on Thr68, phosphorylation of CDC25 (cell division control 25) on Ser 216 and phosphorylation of CDK1 (cyclin-dependent kinase 1) on Tyr 15.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4223-4231
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• 2016

Background: Development of new apoptosis-inducing drugs is a promising trend in anticancer therapy. For this purpose several formamidinoderivatives of doxorubicin were synthesized. The aim of our study was to investigate effects of the five formamidinodoxorubicins in the ES-2 human ovarian clear cell carcinoma line, for comparison with data obtained previously for SKOV-3 human ovarian adenocarcinoma cells, to answer the question of whether and to what extent the histological cell type is a possible determinant of sensitivity to tested anthracyclines. Materials and Methods: In our experimental work the following methods were used: spectrophotometric assays with MTT; fluorimetric assays - double staining with Hoechst 33258 and propidium iodide (PI), measurement of caspase-3, -8, -9 activity, intracellular accumulation of DOX and analogues, estimation of drug uptake, mitochondrial transmembrane potential; flow cytometry - phosphatidylserine (PS) externalization with annexin V-FITC and PI fluorochromes. Results: Effects of the derivatives of doxorubicin were partially linked with the specific type of cancer cell although intracellular accumulation and cellular uptake of DOX and derivatives were similar in both. All of the investigated derivatives were considerably more cytotoxic than DOX. Formamidinodoxorubicins were able to induce caspase-dependent apoptotic cell death in both cell types. Conclusions: All new formamidine derivatives of DOX were able to induce caspase - dependent apoptosis in human ovarian cancer cell lines SKOV-3 and ES-2. Obtained results suggested that formamidine derivatives of DOX may be promising candidates for the prospective chemotherapeutic agents for the two different histological subtypes of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.667-671
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• 2016

Oridonin, an ent-kaurane diterpenoid compound isolated from the traditional Chinese herb Rabdosia rubescens, has shown various pharmacological and physiological effects such as anti-tumor, anti-bacterial, and anti-inflammatory properties. However, the effect of oridonin on human ovarian cancer cell lines has not been determined. In this study, we demonstrated that oridonin inhibited ovarian cancer cell proliferation, migration and invasion in a dose-dependent manner. Furthermore, we showed oridonin inhibited tumor growth of ovarian cancer cells (SKOV3) in vivo. We then assessed mechanisms and found that oridonin specifically abrogated the phosphorylation/activation of mTOR signaling. In summary, our results indicate that oridonin is a potential inhibitor of ovarian cancer by blocking the mTOR signaling pathway.