Abstract 2456: Overexpression of TOM40 (translocase in the outer mitochondrial membrane 40) inhibits the cell proliferation, invasion and migration abilities in ovarian cancer cell lines

Glutamine is one of the main nutrients used by tumor cells for biosynthesis. Therefore, targeted inhibition of glutamine metabolism may have anti-tumorigenic implications. In the present study, we aimed to evaluate the effects of glutamine on ovarian cancer cell growth. Three ovarian cancer cell lines, HEY, SKOV3, and IGROV-1, were assayed for glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis, cell stress, and glucose/glutamine metabolism. Our results revealed that administration of glutamine increased cell proliferation in all three ovarian cancer cell lines in a dose dependent manner. Depletion of glutamine induced reactive oxygen species and expression of endoplasmic reticulum stress proteins. In addition, glutamine increased the activity of glutaminase (GLS) and glutamate dehydrogenase (GDH) by modulating the mTOR/S6 and MAPK pathways. Inhibition of mTOR activity by rapamycin or blocking S6 expression by siRNA inhibited GDH and GLS activity, leading to a decrease in glutamine-induced cell proliferation. These studies suggest that targeting glutamine metabolism may be a promising therapeutic strategy in the treatment of ovarian cancer.

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Cell proliferation of human ovarian cancer is regulated by the opioid growth factor-opioid growth factor receptor axis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00075.2009 ◽

2009 ◽

Vol 296 (6) ◽

pp. R1716-R1725 ◽

Cited By ~ 44

Author(s):

Renee N. Donahue ◽

Patricia J. McLaughlin ◽

Ian S. Zagon

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Growth Factor ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Human Ovarian Cancer ◽

Opioid Growth Factor ◽

Ovarian Cancer Cell Lines

Ovarian cancer is the leading cause of death from gynecological malignancies. Understanding the biology of these tumors, as well as treatment modalities, has been challenging. The opioid growth factor (OGF; [Met5]-enkephalin) and the OGF receptor (OGFr) form an endogenous growth-regulating pathway in homeostasis and neoplasia. In this investigation, we examined the relationship of the OGF-OGFr axis to ovarian cancer, and defined its presence, function, and mechanisms. Using OVCAR-3 and SKOV-3 ovarian cancer cell lines, we found that OGF and OGFr were present and functional. Exogenous OGF was observed to have a dose-dependent, serum-independent, reversible, and receptor-mediated inhibitory action on cell proliferation that was dependent on RNA and protein synthesis. The repressive effect of OGF on cell proliferation also was observed in SW626, CAOV-3, and HEY ovarian cancer cell lines. Endogenous OGF was found to be constitutively produced and tonically active on cell replicative activities, with neutralization of this peptide accelerating cell proliferation. Silencing of OGFr using siRNA technology stimulated cell replication, documenting its integral role. The mechanism of OGF-OGFr action on DNA synthesis was related to the cyclin-dependent kinase inhibitory pathway because knockdown of p16 or p21 in OVCAR-3 cells, and p21 in SKOV-3 cells, eliminated OGF's inhibitory effect on growth. These data are the first to report that the OGF-OGFr system is a native biological regulator of cell proliferation in human ovarian cancer. This information will be important in designing treatment strategies for this deadly disease.

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Implications of HER family inhibition in targeted therapy of ovarian cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13120 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13120-13120

Author(s):

S. L. Bull ◽

J. O. Schorge ◽

M. J. Peyton ◽

L. Xiang ◽

D. S. Miller ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Growth Inhibition ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Her2 Expression ◽

Her Family ◽

Ovarian Cancer Cell Lines

13120 Background: The human epidermal receptor (HER) family couples binding of extracellular ligands to intracellular tyrosine kinase (TK) signal transduction pathways, contributing to cellular proliferation. Overexpression of HER family members has been associated with poor prognosis in ovarian cancer. There is growing evidence to support that none of the individual HER members can be considered as the stand-alone target in ovarian cancer and that cooperation between them influences therapeutic response. To evaluate this receptor cooperation in ovarian cancer our goal was to determine HER family expression and to quantify inhibition of HER1 alone compared to inhibition of HER1/HER2 combined. Methods: HER1, HER2, HER3 and HER4 expression was determined by Western blot in 9 ovarian cancer cell lines. Ovarian cancer cell proliferation was determined after inhibition of HER1 using the monoclonal antibody cetuximab, the TK inhibitor gefitinib, or combination of the two. To quantify the combined inhibition of HER1/HER2, 3 cell lines were selected with variable HER1 and HER2 expression. Cell proliferation was then determined in these 3 cell lines after treatment with cetuximab combined with the monoclonal HER2 antibody, trastuzumab. IC50 values were calculated for all treatment arms and compared. A lung cancer cell line (HCC827), with a HER1 TK mutation and sensitivity to gefitinib and cetuximab, was used as a positive control. Results: HER1 was overexpressed in 3/9 ovarian cancer cell lines, HER2 in 1/9, HER3 in 2/9, and HER4 in 4/9. Minimal to no growth inhibition was seen in the 9 cell lines after blocking HER1 with cetuximab, gefitinib, or the combination of both. In the 3 cell lines selected for HER1 and HER2 expression, there was no growth inhibition achieved despite combining cetuximab with trastuzumab. However, this treatment combination increased resistance in 1 of the 3 cell lines (HCC60), noted to overexpress HER1, 2, and 4. Conclusions: Ovarian cancer has variable HER family expression. No correlation was found between HER1 and HER2 overexpression and response to their targeted inhibition. Our findings support the concept the entire HER family plays a role in ovarian cancer growth and suggest an equilibrium shift of HER heterodimerization may play an important role in maintaining cell signaling. No significant financial relationships to disclose.

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Gedunin, a Novel Natural Substance, Inhibits Ovarian Cancer Cell Proliferation

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181a83135 ◽

2009 ◽

Vol 19 (9) ◽

pp. 1564-1569 ◽

Cited By ~ 39

Author(s):

Siddharth G. Kamath ◽

Ning Chen ◽

Yin Xiong ◽

Robert Wenham ◽

Sachin Apte ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Ovarian Cancer Cells ◽

Expression Data ◽

Ovarian Cancer Cell Lines

The discovery of more active therapeutic compounds is essential if the outcome for patients with advanced-stage epithelial ovarian cancer is to be improved. Gedunin, an extract of the neem tree, has been used as a natural remedy for centuries in Asia. Recently, gedunin has been shown to have potential in vitro antineoplastic properties; however, its effect on ovarian cancer cells is unknown. We evaluated the in vitro effect of gedunin on SKOV3, OVCAR4, and OVCAR8 ovarian cancer cell lines proliferation, alone and in the presence of cisplatin. Furthermore, we analyzed in vitro gedunin sensitivity data, integrated with genome-wide expression data from 54 cancer cell lines in an effort to identify genes and molecular pathways that underlie the mechanism of gedunin action. In vitro treatment of ovarian cancer cell lines with gedunin alone produced up to an 80% decrease in cell proliferation (P < 0.01) and, combining gedunin with cisplatin, demonstrated up to a 47% (P < 0.01) decrease in cell proliferation compared with cisplatin treatment alone. Bioinformatic analysis of integrated gedunin sensitivity and gene expression data identified 52 genes to be associated with gedunin sensitivity. These genes are involved in molecular functions related to cell cycle control, carcinogenesis, lipid metabolism, and molecular transportation. We conclude that gedunin has in vitro activity against ovarian cancer cells and, further, may enhance the antiproliferative effect of cisplatin. The molecular determinants of in vitro gedunin response are complex and may include modulation of cell survival and apoptosis pathways.

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6-shogaol a Active Component from Ginger Inhibits Cell Proliferation and Induces Apoptosis through Inhibition of STAT-3 Translocation in Ovarian Cancer Cell Lines (A2780)

Biotechnology and Bioprocess Engineering ◽

10.1007/s12257-018-0502-3 ◽

2019 ◽

Vol 24 (3) ◽

pp. 560-567 ◽

Cited By ~ 4

Author(s):

Ting Liang ◽

Ying He ◽

Yuhua Chang ◽

Xiantong Liu

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Cancer Cell ◽

Active Component ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Ovarian Cancer Cell Lines

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E2F8 Induces Cell Proliferation and Invasion through the Epithelial–Mesenchymal Transition and Notch Signaling Pathways in Ovarian Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21165813 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5813

Author(s):

Kyung Jin Eoh ◽

Hee Jung Kim ◽

Jong Woo Lee ◽

Lee Kyung Kim ◽

Sun-Ae Park ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Cancer Cell ◽

Epithelial Mesenchymal Transition ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Mesenchymal Transition ◽

Ovarian Cancer Cell Lines

Background: Despite the recent research implicating E2F8 (E2F Transcription Factor 8) in cancer, the role of E2F8 in the progression of ovarian cancer has remained unclear. Hence, we explored the bio-functional effects of E2F8 knockdown on ovarian cancer cell lines in vitro and in vivo. Methods: The expression of E2F8 was compared between ovarian cancer and noncancer tissues, and its association with the progression-free survival of ovarian cancer patients was analyzed. To demonstrate the function of E2F8 in cell proliferation, migration, and invasion, we employed RNA interference to suppress E2F8 expression in ovarian cancer cell lines. Finally, the effect of E2F8 knockdown was investigated in a xenograft mouse model of ovarian cancer. Results: Ovarian cancer tissue exhibited significantly higher E2F8 expression compared to that of normal ovarian tissue. Clinical data showed that E2F8 was a significant predictor of progression-free survival. Moreover, the prognosis of the ovarian cancer patients with high E2F8 expression was poorer than that of the patients with low E2F8 expression. In vitro experiments using E2F8-knockdown ovarian cancer cell lines demonstrated that E2F8 knockdown inhibited cell proliferation, migration, and tumor invasion. Additionally, E2F8 was a potent inducer and modulator of the expression of epithelial–mesenchymal transition and Notch signaling pathway-related markers. We confirmed the function of E2F8 in vivo, signifying that E2F8 knockdown was significantly correlated with reduced tumor size and weight. Conclusions: Our findings indicate that E2F8 is highly correlated with ovarian cancer progression. Hence, E2F8 can be utilized as a prognostic marker and therapeutic target against ovarian malignancy.

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LncRNA LINC00665 promotes ovarian cancer cell proliferation and inhibits apoptosis via targeting miR-181a-5p/FHDC

10.21203/rs.3.rs-389237/v1 ◽

2021 ◽

Author(s):

Suli Wang ◽

yingchun Wang ◽

Jinhua Wang ◽

Jin Lu ◽

Ke Li

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Inhibitory Effect ◽

Cell Counting ◽

Luciferase Reporter ◽

Ovarian Cancer Cell Lines ◽

Vital Effect ◽

And Migration

Abstract Previous reports indicate that LINC00665, a lincRNA, which is a naturally occurring long intergenic non-coding RNA exerts vital effect in a variety of cancers. Herein, we explore the role of LINC00665 in ovarian cancer. RT-qPCR was taken into the experiment to determine the expression level of LINC00665. Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, transwell, and EdU are employed to evaluate the effect of LINC00665 on cell proliferation, apoptosis, and migration in SKOV-3 and OVCAR-3 cells. The axis of LINC00665 and its specific miRNA, the miRNA target gene is explored in dual-luciferase reporter assay. Firstly, we find that LINC00665 is upregulated in ovarian cancer cell lines. Furthermore, not only the cell viability and in SKOV-3 and OVCAR-3 was reduced by LINC00665 knockdown but also cell proliferation and migration were inhibited. Afterwards, the bioinformatics analysis suggested that LNC00665 specifically binds to miR-181a-5p. Then, several studies confirmed that LINC00665 downregulated the miR-181a-5p in SKOV-3 and OVCAR-3 cells. The knockdown of miR-181a-5p evidently reverses the inhibitory effect of sh-LINC00662. Besides, FH2 Domain Containing 1 (FHDC1) has been proved to deed as an effective target of miR-181a-5p. In conclusion, the knockdown of LINC00665 facilitates ovarian cancer via development by sponging miR-181a-5p and upregulating FHDC1 expression.

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