Ovarian Cancer Cell Lines HO8910 Research Articles

Downregulation of vimentin expression increased drug resistance in ovarian cancer cells.

Cisplatin and other platinum-based drugs have been widely used in the treatment of ovarian cancer, but most patients acquire the drug resistance that greatly compromises the efficacy of drugs. Understanding the mechanism of drug resistance is important for finding new therapeutic approaches. In the present study, we found that the expression of vimentin was downregulated in drug-resistant ovarian cancer cell lines A2780-DR and HO-8910 as compared to their respective control cells. Overexpression of vimentin in A2780-DR cells markedly increased their sensitivity to cisplatin, whereas knockdown of vimentin in A2780, HO-8910-PM and HO-8910 cells increased the resistance to cisplatin, demonstrating that vimentin silencing enhanced cisplatin resistance in ovarian cancer cells. Quantitative proteomic analysis identified 95 differentially expressed proteins between the vimentin silenced A2780 cells (A2780-VIM-KN) and the control cells, in which downregulation of endocytic proteins and the upregulation of exocytotic proteins CHMP2B and PDZK1 were proposed to contribute the decreased cisplatin accumulation in vimentin knockdown cells. Silencing of vimentin induced upregulation of cancer stem cell markers and both A2780-DR and A2780-VIM-KN cells were more facile to form spheroids than control cells under serum-free culture condition. Our results also revealed that vimentin knockdown increased the 14-3-3 mediated retention of Cdc25C in the cytoplasm, leading to inactivation of Cdk1 and the prolonged G2 phase arrest that allowed the longer period of time for cells to repair cisplatin-damaged DNA. Taken together, we demonstrated that vimentin silencing enhanced cells' resistance to cisplatin via prolonged G2 arrest and increased exocytosis, suggesting that vimentin is a potential target for treatment of drug resistant ovarian cancer.

Overexpression of CARMA3 is associated with advanced tumor stage, cell cycle progression, and cisplatin resistance in human epithelial ovarian cancer.

CARD recruited membrane associated protein 3 (CARMA3) overexpression has been found in several human cancers. However, its expression pattern and biological roles in human ovarian cancers are not clear. In this study, we examined the expression pattern of CARMA3 in 101 ovarian cancer specimens. We found that 52 (51.5 %) showed CARMA3 overexpression. CARMA3 overexpression positively correlated with tumor histology and advanced FIGO stage. CARMA3 depletion in ovarian cancer cell lines A2780 and HO8910 inhibited ovarian cancer cell proliferation and blocked cell cycle progression. CARMA3 depletion also sensitized ovarian cancer cells to cisplatin-induced cytotoxicity. In addition, Western blot showed that CARMA3 depletion downregulated cyclin D1, cyclin E, and Bcl-2 levels. In conclusion, our data provides evidence that CARMA3 is overexpressed in ovarian cancers and associated with advanced stage. CARMA3 regulates the ovarian cancer cell proliferation, cell cycle progression, and chemoresistance.

Effect and mechanism of gene therapy of lentivirus mediated RhoA shRNA on ovarian cancer xenograft in vivo

To investigate treatment effects of lentivirus mediated RhoA short hairpin RNA (shRNA) on xenograft tumor of ovarian cancer in nude mice in vivo and the underlying mechanism. Human ovarian cancer cell line HO8910 were inoculated to establish subcutaneous xenograft model of human ovarian cancer. Tumor-bearing nude mice were assigned randomizely to three groups: Lenti-RhoA-sh group, Lenti- negative control (NC) group and phosphate buffered saline (PBS) group.lentivirus mediated RhoA shRNA, negative control lentivirus and PBS were respectively injected in the three groups. Effects of treatment were observed by tumor growth curve, tumor volume, tumor weight, and tumor inhibition rate. Xenograft tissues and liver, spleen, lung, and renal tissues were examined by hematoxylin and eosin (HE) staining or were detected by streptavidin-perosidase(SP)immunochemical method. The changes of RhoA gene expression in xenograft tissues after lentivirus mediated RhoA shRNA treated were also detected by real-time qPCR, immunochemistry and Western blot assay. Cell apoptosis in xenograft tissues were examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and apoptotic index (AI) were counted. Compared with Lenti-NC group and PBS group, the growth speed of xenograft in Lenti-RhoA-sh group delayed significantly after injection 9 days (P < 0.01) . Tumor volume (338 ± 114) mm(3) decreased significantly in the Lenti-RhoA-sh group when compared with those in Lenti-NC group (1190 ± 332) mm(3) and PBS group (1101 ± 396) mm(3) (P < 0.01) . Tumor weight (0.23 ± 0.11) g decreased significantly in the Lenti-RhoA-sh group when compared with Lenti-NC group (0.79 ± 0.19) g and PBS group (0.74 ± 0.17) g (P < 0.01) . Real-time qPCR result shown that the expression of RhoA mRNA (0.30 ± 0.05) decreased significantly in the Lenti-RhoA-sh group compared with Lenti-NC group (0.95 ± 0.06) and PBS group(1.00 ± 0.11; P < 0.01) .Western blot result showed that the expression level of RhoA protein decreased significantly in the Lenti-RhoA-sh group (0.14 ± 0.06) compared with those in Lenti-NC group(0.78 ± 0.14) and PBS group (0.75 ± 0.13;P < 0.01). TUNEL staining displayed that AI significantly increased in the Lenti-RhoA-sh group (20.9 ± 3.4) % compared with those in Lenti-NC group (5.2 ± 2.0) % and PBS group (6.0 ± 2.1) % (P < 0.01). Lentivirus mediated RhoA shRNA may be effectively down-regulate of the expression of RhoA, inhibit the growth of subcutaneous xenograft tumor of ovarian cancer in nude mice by increasing the cell apoptosis.

The combined effect of survivin-targeted shRNA and emodin on the proliferation and invasion of ovarian cancer cells

Survivin has been shown to be highly expressed in ovarian cancers, but not normal ovarian tissue, which makes it an attractive target for ovarian cancer treatment. Emodin is a traditional Chinese medicine that has been found to inhibit proliferation and induce apoptosis in ovarian cancer cells. Thus, in our study, we combined survivin-targeted shRNA (sur-shRNA) with emodin and tested the effects of this combination on ovarian cancer cells to identify more effective therapeutics against ovarian cancer. A sur-shRNA plasmid was constructed and transfected into the ovarian cancer cell lines SKOV3 and HO8910, and the cells were cultured for 24 h. The cells were then treated with emodin for specific time periods and assessed for viability and apoptosis using the MTT assay and flow cytometry, respectively. Cell invasion was also measured using a Matrigel invasion assay. The shRNA specific for survivin effectively reduced the expression of survivin at the mRNA and protein levels in SKOV3 and HO8910 cells. Both emodin and shRNA-mediated knockdown of survivin significantly inhibited cell proliferation, induced apoptosis, and suppressed invasion in SKOV3 and HO8910 cells (P<0.05). Moreover, the combination of the agents significantly enhanced these effects (P<0.05). We found that the combination of sur-shRNA and emodin could be effective in the treatment of ovarian cancer.

English

To study the effects of Mesima Reishi UE-1 on the metastatic phenotype of the human ovarian cancer cell line HO8910. HO8910 cells were pretreated with different concentration of Mesima Reishi UE-1&nbsp;in vitro. Using cell proliferation assay, spreading and adhesion assay, cell migration and invasion assay, zymography, immunocytochemical staining and RT-PCR, we examined the effects of Mesima Reishi UE-1 on cell proliferation, motility, adhesion and expression of MMP-2, 9&nbsp;invitro. Mesima Reishi UE-1 directly inhibited HO8910 cell proliferation&nbsp;in vitro. And pretreated with different concentrations of Mesima Reishi UE-1, HO8910 cells motility, adhesion and invasion were inhibited significantly. The activity of MMP-9 was inhibited in a dose-dependent manner. The protein and mRNA expression of MMP-2, 9 were also inhibited. Mesima Reishi UE-1 suppresses invasion of human ovarian cancer cells&nbsp;in vitro. &nbsp; Key words:&nbsp;Mesima Reishi UE-1, polysaccharides, human ovarian cancer, tumor invasion, matrix metalloproteinase.

Progesterone protects ovarian cancer cells from cisplatin-induced inhibitory effects through progesterone receptor membrane component 1/2 as well as AKT signaling

Progesterone, also known as P4 (pregn-4-ene-3, 20-dione), is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species. Despite the physiological effects, P4 is also effective for the treatment of numerous pathological states, such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus as well as cancer. Considering the hormone microenvironment of gynecological cancers, P4 should be particularly noted in ovarian cancer. The present study demonstrated that P4 protected the ovarian cancer cell line HO-8910 from cisplatin (CDDP)-induced cell cycle arrest and restored the cell migratory capability following treatment of CDDP. Mechanistically, both progesterone receptor membrane component 1 (PGRMC1) and the progesterone receptor (PGR) were decreased in the cells treated with CDDP plus P4, while the level of progesterone receptor membrane component 2 (PGRMC2) was significantly elevated. Reversely, in the HO-8910 cells treated with CDDP alone, levels of both PGRMC1 and PGR were increased while the level of PGRMC2 was decreased. In addition to the receptor expression profile, the PI3K/AKT signaling pathway was also involved in the action of P4 in the CDDP-resistant HO-8910 cells, and a chemical inhibitor for PI3K, LY294002, significantly abolished the anti-apoptotic effect of P4. Consequently, the addition of a PI3K inhibitor to CDDP-based chemotherapy may have a more beneficial application for ovarian cancer therapy.

Abstract 4692: ARL4C, a novel ovarian cancer-related gene, its down-regulated predicts poor survival in ovarian cancer.

Abstract Purpose: To identify the genes involved in ovarian cancer progression and elucidate their biological actions in ovarian cancer. Experimental Design: Comparative genomic hybridization (CGH) was employed to screen the chromosome fragments with different copy numbers between the ovarian cancer cell line HO-8910 and its highly metastatic cell subline HO-8910PM. Fluorescent in situ hybridization (FISH) via biotin-labeled BAC clone probes was used to validate the results of CGH. Using gene expression microarray, differentially expressed genes on the target chromosome fragment were compared between the two cell lines. Lentiviral-mediated transfection was used to investigate the effects of candidate gene over-expression or knockdown on colony formation, proliferation and motility of ovarian cancer cells. Two hundred twelve epithelial ovarian cancer samples were analyzed for mRNA expression of candidate gene using RT-PCR. Associations of the gene expression with clinicopathological factors, progression free and overall survival were evaluated. Results: Chromosome fragment 2q36.1-37.3 was found hemizygous deletion in HO-8910PM cells by CGH and FISH. Comparing gene expression data, we identified ARL4C, located on chromosome 2q37.1, to be down-regulated in the HO-8910PM cells, compared with the HO-8910 cells. Western blot showed ARL4C expression was low/null in most ovarian cancer cell lines, including the HO-8910PM cells. ARL4C over-expression or knockdown had no obvious effect on colony formation and cell proliferation, but negatively regulated cell motility. ARL4C over-expression suppressed ovarian cancer cells migration and invasion. Inversely, ARL4C knockdown promoted ovarian cancer cells migration. Clinicopathologic studies further supported the relevance of ARL4C in ovarian cancers. Patients with medium or high levels of ARL4C mRNA were at lower risk for death, compared to those with low levels (HR, 0.45; 95% C.I., 0.27-0.76; P=0.003 for mid levels; and HR, 0.58; 95% C.I., 0.35-0.96; P = 0.035 for high levels) after adjusting for age, disease stage, tumor grade, histologic type and residual tumor size. Kaplan-Meier survival analysis demonstrated similar results. Conclusions: ARL4C is a novel ovarian cancer related gene that inhibits cell motility. It seems to play a protective role in cancer progression and is an independent prognostic factor for patient with ovarian cancer. More studies are needed to further elucidate the molecular mechanisms of ARL4C in ovarian cancer progression. Citation Format: Dan Su, Shenhau Xu, Haiyan Xu, Yun Gao, Jianguo Feng, Min Luo, Lisha Ying, Nengming Lin, Dionyssios Katsaros, Herbert Yu. ARL4C, a novel ovarian cancer-related gene, its down-regulated predicts poor survival in ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4692. doi:10.1158/1538-7445.AM2013-4692

Poly(ethylene glycol)-cross linked poly(methyl vinyl ether-co-maleic acid)hydrogels for three-dimensional human ovarian cancer cell culture

In this work, three kinds of poly(ethylene glycol)-cross linked poly(methyl vinyl ether-co-maleic acid) hydrogels, Gel-1, Gel-2, and Gel-3 with different elastic modulus of 105,100Pa, 12,020Pa, and 2191Pa were designed for simulating respectively the mechanical strength of stiffer metastasis bone sites, cancerous soft tissue, and BME or collagen, and were evaluated in three-dimensional (3D) culture of human ovarian cancer cell line HO8910. The proliferation, adhesion, migration, and invasion of ovarian cells HO8910 in these three kinds of hydrogels were systematically investigated and compared with two commercial hydrogels BME and collagen I. Hydrogels Gel-1 and Gel-2 with higher elastic modulus showed a better cytocompatibility and remarkably supported the proliferation of ovarian cancer cell line HO8910 and the formation of multicellular spheroids (MCS) in a 3D model. The mechanical properties of hydrogels played a crucial role in responses of HO8910 cells. The hydrogels Gel-1 and Gel-2 are also the potential 3D culture matrix materials for cancer cell culture.

Effects of Sodium Valproate on the Growth of Human Ovarian Cancer Cell Line HO8910

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 G0/ G1 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.

M345 THE EFFECTS OF MIRNA-7 ON THE INVASION AND PROLIFERATION IN HUMAN OVARIAN CANCER CELL LINE HO-8910 AND HO-8910PM CELLS

International Journal of Gynecology & ObstetricsVolume 119, Issue S3 p. S641-S642 Poster presentations M345 THE EFFECTS OF MIRNA-7 ON THE INVASION AND PROLIFERATION IN HUMAN OVARIAN CANCER CELL LINE HO-8910 AND HO-8910PM CELLS L. Qiu, L. QiuSearch for more papers by this authorX. Zhou, X. ZhouSearch for more papers by this author L. Qiu, L. QiuSearch for more papers by this authorX. Zhou, X. ZhouSearch for more papers by this author First published: 22 October 2012 https://doi.org/10.1016/S0020-7292(12)61536-7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume119, IssueS3Abstracts of XX FIGO World Congress of Gynecology and ObstetricsOctober 2012Pages S641-S642 RelatedInformation

Expression of KiSS-1 in Epithelial Ovarian Cancer and its Role in Metastasis

Objectives To study expression of KiSS-1 and its role in migration and invasion of ovarian cancer (OC). Methods Expression of KiSS-1 was detected in tissue of 46 cases of OC and 17 cases of benign ovarian neoplasm by immunohistochemistry examination. Human OC cell line HO8910 was transfected by pcDNA3-KiSS-1 vector. The cell proliferation and invasion properties were detected by RT-RCR, MTT, clone formation rate and Boyden Chamber invasion assay. Results (1) Immunostaining showed that expression of KiSS-1protein was significantly higher in OC than that in benign ovarian tumor (P&lt;0.05). (2) KiSS-1 expression was significantly higher in cases of advanced stage and with lymphatic metastasis (P&lt;0.05). KiSS-1 expression was significantly lower in clear cell cancer compared with other histologic types (P&lt;0.05). (3)KiSS-1 gene was successfully integrated into the genomic DNA of ovarian cancer cell line HO8910. Boyden Chamber invasion assay revealed that the number of cells invading through the Matrigel filter was significantly decreased in the transfected group compared with the non-transfected. No differences were observed in cell proliferation between the two groups. Conclusion There was over expression of KiSS-1 in OC compared with that in benign ovarian tumor. The KiSS-1 gene could suppress HO8910 invasion in vitro. To elucidate the contradiction effects of metastasis suppressor genes KiSS-1in vivoandin vitroneeds deeper research.

Effects of PTEN over-expression on phosphatidyl inositol 3-kinase/protein kinase B signal pathway in ovarian epithelial cancer cells

To evaluate the effect of exogenous wild PTEN gene stable transfected into human ovarian cancer cell line HO-8910 on phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (Akt) signal pathway and cells proliferation. Wild-type PTEN recombinant eukaryotic expression plasmid was constructed and then was transfected into HO-8910 cells by lipofectamine 2000. The expression of PTEN, Akt1, Akt2, PI3K mRNA and protein of PTEN were tested by reverse transcription (RT)-PCR and Western blot. The proliferation of HO-8910 after wild PTEN gene transfected was measured by methyl thiazolyl tetrazolium (MTT). Wild-type PTEN gene was successfully transfected into HO-8910 cells. The results of RT-PCR and western bolt showed that there were the significant expression high level of PTEN mRNA and protein after infected by wild-PTEN plasmid than those in the control [(17,372 ± 23) vs. (39 ± 1) vs. (78 ± 4) copies/ml, P < 0.05]. While the expression of mRNA of Akt1, Akt2 and PI3K were decreased clearly than those in the control [(28 ± 2) vs. (115 ± 5), (7 ± 1) vs. (18 ± 2), (61 ± 2) vs. (84 ± 2) copies/ml, all P < 0.05]. The proliferation rate of HO-8910 cells was obviously slower than those in the control (90 158 ± 47 vs. 148,251 ± 65 vs. 250,115 ± 62, P < 0.05). Transfection of PTEN may increase the expression of PTEN and inhibit the proliferation of HO-8910 cells, in which PI3K/Akt signal pathway is inhibit significantly.

Effect of dexamethasone and transforming growth factor β&lt;SUB&gt;1&lt;/SUB&gt; on expression of plasminogen activator inhibitor-1 in human ovarian cancer cell line HO-8910

Effect of dexamethasone and transforming growth factor β&lt;SUB&gt;1&lt;/SUB&gt; on expression of plasminogen activator inhibitor-1 in human ovarian cancer cell line HO-8910

Dexamethasone enhances cell resistance to chemotherapy by increasing adhesion to extracellular matrix in human ovarian cancer cells

Glucocorticoids (GCs) are widely used as co-medication in the therapy of solid malignant tumors to relieve some of the side effects of chemotherapeutic drugs. However, recent studies have shown that GCs could render cancer cells more resistant to cytotoxic drug-induced apoptosis, but the mechanism is largely unknown. In the present study, we found that the treatment of human ovarian cancer cell lines HO-8910 and SKOV3 with synthetic GCs dexamethasone (Dex) significantly increased their adhesion to extracellular matrix (ECM) and their resistance to apoptosis induced by cytotoxic drugs cisplatin and paclitaxel. Dex also increased the protein levels of adhesion molecules integrins beta1, alpha 4, and alpha 5 in HO-8910 cells. The neutralizing antibody against integrin beta1 prevented Dex-induced adhesion and significantly abrogated the protective effect of Dex toward cytotoxic agents. We further found that transforming growth factor-beta1 (TGF-beta1) alone not only increased cell adhesion and cell survival of HO-8910 cells in the presence of cisplatin, but also had synergistic pro-adhesion and pro-survival effects with Dex. Moreover, TGF-beta1-neutralizing antibody that could block TGF-beta1-induced cell adhesion and apoptosis resistance markedly abrogated the synergistic pro-adhesion and pro-survival effects of Dex and TGF-beta1. Finally, we further demonstrated that Dex could up-regulate the expression of TGF-beta receptor type II and enhance the responsiveness of cells to TGF-beta1. In conclusion, our results indicate that increased adhesion to ECM through the enhancement of integrin beta1 signaling and TGF-beta1 signaling plays an important role in chemoresistance induced by GCs in ovarian cancer cells.

Microarray analysis of gene expression in the ovarian cancer cell line HO-8910 with silencing of the ZNF217 gene

Zinc-finger protein 217 (ZNF217), which is overexpressed during cancer progression, can promote tumor cell immortalization. To examine the function of ZNF217, a global expression profile was carried out using Affymetrix Gene Chip analysis with HG-U133 plus 2.0 arrays in the ovarian cancer cell line HO-8910 after silencing of the ZNF217 gene. The results were analyzed using the Gene Ontology program to investigate the functional network affected by ZNF217 in ovarian cancer cells. Changes in the mRNA expression of the affected genes were confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the ZNF217 gene is a key regulator of ovarian cancer, as the silencing of ZNF217 resulted in significant down-regulation by at least 8-fold of 164 genes in the HO-8910 cell line compared to non-silenced control cells. Among these down-regulated genes were ALOX15, CD1D, FXYD3, GAS6, KRT4, LIN7B, MMP-24, PDZK1, PEX6, PRSS8, SLC2A9, STRN and WFDC2. Down-regulation was confirmed by real-time RT-PCR after the silencing of ZNF217 (p<0.05). The results suggest that ZNF217 plays a central role in malignant processes in ovarian cancer.

Effects of WWOX gene transfection on cell growth of epithelial ovarian cancer

To study the effects of anti-oncogene WWOX on cell growth of epithelial ovarian cancer,in order to find a new approach of gene therapy for ovarian cancer. A eukaryotic expression vector containing WWOX was transfected into ovarian cancer cell line HO8910 in vitro (recombinant plasmid group), and positive cell clones were selected and amplified. Expression of WWOX protein was detected by western blot. Untransfected cell (blank contrast group) and transfected empty plasmid cell (empty plasmid group) were served as control groups. In vitro, the biology effect of WWOX on HO8910 cell was analyzed through the methyl thiazolyl tetrazolium test, transwell chamber cell invasion assay in vitro, agarose clony-formation and flow cytometry. In vivo, the cell of transfection was transplanted intraperitoneally in to BALB/c nude mice. The survival time and growth ability of nude mice were observed. (1) Recombinant plasmid group cell could steadily express WWOX protein, while in empty plasmid group and blank control group the expression of WWOX protein were not detected. (2) The growth rate of recombinant plasmid group cell was inhibited. (3) The agarose clony-formation rate of recombinant plasmid group (19.8%) was significantly lower than that of the empty plasmid group (54.5%) and blank control group (56.0%, P < 0.05). (4) Flow cytometry showed that (72.08 +/- 0. 39)% of cells was arrested at G0/G1 stage in recombinant plasmid group, while in empty plasmid group and blank control group G0/G1 stage cells were at (41.02 +/- 1.08)% and (39.31 +/- 0.67)% (P < 0.05). (5) In vitro invasion assay showed that invasion cell number in recombinant plasmid group (89.7 +/- 3.1) was not significantly different from that of empty plasmid group (91.2 +/- 1.3) and blank control group (91.4 +/- 1.3, P > 0.05). (6) In vivo test in nude mice showed that WWOX gene could inhibit tumor growth of the HO8910 cells. Tumor suppressor gene WWOX could interfere with the cell cycles of ovarian cancer cell and inhibit cell proliferation. As a new valuable tool, it promises to have application in the gene therapy of ovarian cancer.

Identification of metastasis-associated proteins of ovarian cancer by proteomics

To investigate the differenal protein expression profiles of ovarian tumor cell lines with distinct metastatic abilities. The ovarian cancer cell line HO8910 and HO8910pm, derived from same parental cells but exhibited different metastatic ability, were investigated by two-dimensional gel electrophoresis (2-DE)-MALDI-TOF-MS proteomic approach. Thirty-nine proteins were detected by 2-DE to have expression disparity levels over 2 folds between two cell lines. Eighteen of them were identified by MALDI-TOF-MS. The proteins are involved in apoptosis, extra cellular matrix (ECM), cytoskeleton, growth factor, glycolysis, protein metabolism and immune system. The data are valuable for the identification of differentially expressed proteins involved in the biological behavior of human ovarian cancer.

PGC-1α induces apoptosis in human epithelial ovarian cancer cells through a PPARγ-dependent pathway

Peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha) coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the role of PGC-1alpha in the induction of apoptosis in human epithelial ovarian cancer cells. The PGC-1alpha mRNA level between human ovaries and human ovarian epithelial tumors was examined by quantitative RT-PCR. Less PGC-1alpha expression was found in the surface epithelium of malignant tumors compared with normal ovaries. Overexpression of PGC-1alpha in human epithelial ovarian cancer cell line Ho-8910 induced cell apoptosis through the coordinated regulation of Bcl-2 and Bax expression. Microarray analyses confirmed that PGC-1alpha dramatically affected the apoptosis-related genes in Ho-8910 cells. Mitochondrial functional assay showed that the induction of apoptosis was through the terminal stage by the release of cytochrome c. Furthermore, PGC-1alpha-induced apoptosis was partially, but not completely, blocked by PPARgamma antagonist (GW9662), and suppression of PPARgamma expression by siRNA also inhibited PGC-1alpha-induced apoptosis in Ho-8910 cells. These data suggested that PGC-1alpha exerted its effect through a PPARgamma-dependent pathway. Our findings indicated that PGC-1alpha was involved in the apoptotic signal transduction pathways and downregulation of PGC-1alpha may be a key point in promoting epithelial ovarian cancer growth and progression.

The Effect of 17 Sesquiterpenes on Cell Viability and Telomerase Activity in the Human Ovarian Cancer Cell Line HO-8910

Using the MTT assay and the telomeric repeat amplification protocol (TRAP)-based PCR-ELISA assay, the cytotoxicity and telomerase inhibiting ability of 17 sesquiterpenes (extracted from Chinese herbs) were tested in the human ovarian cancer cell line HO-8910. The results indicated that seven sesquiterpenes inhibited cell proliferation without having an effect on telomerase activity; two sesquiterpenes inhibited neither cell proliferation nor telomerase activity; and the other eight sesquiterpenes inhibited both cell proliferation and telomerase activity to a certain extent. Without exception, none of these 17 sesquiterpenes could only inhibit telomerase activity without inhibiting cell proliferation. This indicated that the telomerase inhibiting activity is not a universal mechanism for all anticancer drugs but is only one of several possible mechanisms. The structure-activity relationships of 5 groups of sesquiterpenes are also discussed. This study may help to develop anticancer drugs.

Impact of different pressures and exposure times of a simulated carbon dioxide pneumoperitoneum environment on proliferation and apoptosis of human ovarian cancer cell lines

This study aimed too evaluate the proliferation and apoptosis of human ovarian cancer cell lines HO8910 and SKOV3 after exposure to a simulated laparoscopic carbon dioxide (CO2) pneumoperitoneum environment at different pressures and lengths of exposure time. The effects of the simulated laparoscopic CO2 pneumoperitoneum environment at different CO2 pressures (0-16 mmHg) and exposure times (1-4 h) on tumor cell growth and apoptosis were assessed by 3-[4,5-Dimethylthiazol]-2; 5-diphenyltetrazolium bromide (MTT) chromometry and proliferative index (PI) staining or Annexin V and PI double-staining flow cytometry. Cells cultured in a standard environment were used as the control group. In this study, HO8910 cell growth tended to slow down with the increase in CO2 pressure and exposure time. A significantly lower PI was observed at 72 h of culture after exposure to both 8 and 16 mmHg of pressure, as compared with the control and 0 mmHg pressure group (p < 0.05). The PI of SKOV3 cells tended to decline after exposure. Significantly lower PI was observed in the group with exposure to 16 mmHg for 4 h over a 72-h period, as compared with the control groups exposed to 0 mmHg (p < 0.05). The inhibition of cell growth was associated with an increase in the proportion of cells at stage G1. The apoptotic index and the percentage of apoptotic cells tended to increase with an increase in pressure and a prolonged time of exposure. The results suggest inhibited cell proliferation and increased cell apoptosis of human ovarian cancer cells were positively related to CO2 pressure and exposure time.