scholarly journals The Anti-Proliferative Effect of PI3K/mTOR and ERK Inhibition in Monolayer and Three-Dimensional Ovarian Cancer Cell Models

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 395
Author(s):  
Elizabeth Dunn ◽  
Kenny Chitcholtan ◽  
Peter Sykes ◽  
Ashley Garrill
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Alternative Pathway ◽  
Three Dimensional ◽  
Cell Aggregates ◽  
Erk Inhibition ◽  
Inhibitor Combination ◽  
Dimensional Cell

Most ovarian cancer patients are diagnosed with advanced stage disease, which becomes unresponsive to chemotherapeutic treatments. The PI3K/AKT/mTOR and the RAS/RAF/MEK/ERK kinase signaling pathways are attractive targets for potential therapeutic inhibitors, due to the high frequency of mutations to PTEN, PIK3CA, KRAS and BRAF in several ovarian cancer subtypes. However, monotherapies targeting one of these pathways have shown modest effects in clinical trials. This limited efficacy of the agents could be due to upregulation and increased signaling via the adjacent alternative pathway. In this study, the efficacy of combined PI3K/mTOR (BEZ235) and ERK inhibition (SCH772984) was investigated in four human ovarian cancer cell lines, grown as monolayer and three-dimensional cell aggregates. The inhibitor combination reduced cellular proliferation in a synergistic manner in OV-90 and OVCAR8 monolayers and in OV-90, OVCAR5 and SKOV3 aggregates. Sensitivity to the inhibitors was reduced in three-dimensional cell aggregates in comparison to monolayers. OV-90 cells cultured in large spheroids were sensitive to the inhibitors and displayed a robust synergistic antiproliferative response to the inhibitor combination. In contrast, OVCAR8 spheroids were resistant to the inhibitors. These findings suggest that combined PI3K/mTOR and ERK inhibition could be a useful strategy for overcoming treatment resistance in ovarian cancer and warrants further preclinical investigation. Additionally, in some cell lines the use of different three-dimensional models can influence cell line sensitivity to PI3K/mTOR and RAS/RAF/MEK/ERK pathway inhibitors.

scholarly journals Resveratrol, Acetyl-Resveratrol, and Polydatin Exhibit Antigrowth Activity against 3D Cell Aggregates of the SKOV-3 and OVCAR-8 Ovarian Cancer Cell Lines

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Simon J. Hogg ◽  
Kenny Chitcholtan ◽  
Wafaa Hassan ◽  
Peter H. Sykes ◽  
Ashley Garrill
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Cell Aggregates ◽  
Signalling Molecules ◽  
Ovarian Cancer Cell Lines ◽  
Her 2

Resveratrol has aroused significant scientific interest as it has been claimed that it exhibits a spectrum of health benefits. These include effects as an anti-inflammatory and an antitumour compound. The purpose of this study was to investigate and compare any potential antigrowth effects of resveratrol and two of its derivatives, acetyl-resveratrol and polydatin, on 3D cell aggregates of the EGFR/Her-2 positive and negative ovarian cancer cell lines SKOV-3 and OVCAR-8, respectively. Results showed that resveratrol and acetyl-resveratrol reduced cell growth in the SKOV-3 and OVCAR-8 in a dose-dependant manner. The growth reduction was mediated by the induction of apoptosis via the cleavage of poly(ADP-ribose) polymerase (PARP-1). At lower concentrations, 5 and 10 µM, resveratrol, acetyl-resveratrol, and polydatin were less effective than higher concentrations, 50 and 100 µM. In SKOV-3 line, at higher concentrations, resveratrol and polydatin significantly reduced the phosphorylation of Her-2 and EGFR and the expression of Erk. Acetyl-resveratrol, on the other hand, did not change the activation of Her-2 and EGFR. Resveratrol, acetyl-resveratrol, and polydatin suppressed the secretion of VEGF in a dose-dependant fashion. In the OVCAR-8 cell line, resveratrol and acetyl-resveratrol at 5 and 10 µM increased the activation of Erk. Above these concentrations they decreased activation. Polydatin did not produce this effect. This study demonstrates that resveratrol and its derivatives may inhibit growth of 3D cell aggregates of ovarian cancer cell lines via different signalling molecules. Resveratrol and its derivatives, therefore, warrant furtherin vivoevaluation to assess their potential clinical utility.

scholarly journals Three-Dimensional Cellular Arrangement in Epithelial Ovarian Cancer Cell Lines TOV-21G and SKOV-3 is Associated with Apoptosis-Related miRNA Expression Modulation

2018 ◽  
Vol 11 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Aline Brito de Lima ◽  
Luciana Maria Silva ◽  
Nikole Gontijo Gonçales ◽  
Maria Raquel Santos Carvalho ◽  
Agnaldo Lopes da Silva Filho ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mirna Expression ◽  
Ovarian Cancer Cell ◽  
Three Dimensional ◽  
Epithelial Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Lines ◽  
Expression Modulation

scholarly journals Niosome-encapsulated balanocarpol: compound isolation, characterisation, and cytotoxicity evaluation against human breast and ovarian cancer cell lines

2020 ◽  
Vol 31 (19) ◽  
pp. 195101 ◽  
Author(s):  
Mohammad A Obeid ◽  
Siti Aisya S Gany ◽  
Alexander I Gray ◽  
Louise Young ◽  
John O Igoli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Breast ◽  
Breast And Ovarian Cancer ◽  
Ovarian Cancer Cell Lines

scholarly journals Difference between genomic actions of estrogen versus raloxifene in human ovarian cancer cell lines

Oncogene ◽  
2008 ◽  
Vol 27 (19) ◽  
pp. 2737-2745 ◽  
Author(s):  
H Sasaki ◽  
J Hayakawa ◽  
Y Terai ◽  
M Kanemura ◽  
A Tanabe-Kimura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Ovarian Cancer ◽  
Human Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Lines

scholarly journals miR-214 promotes radioresistance in human ovarian cancer cells by targeting PETN

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Qin Zhang ◽  
Shuxiang Zhang
Keyword(s):  
Ovarian Cancer ◽  
Ionizing Radiation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Ovarian Cancer Cell Lines ◽  
Cancer Tissues

Ovarian cancer is one of the leading causes of death among gynecological malignancies. Increasing evidence indicate that dysregulation of microRNAs (miRNAs) plays an important role in tumor radioresistance. The aim of the present study is to investigate whether microRNA-214 (miR-214) was involved in radioresistance of human ovarian cancer. Here, we showed that miR-214 was significantly up-regulated in ovarian cancer tissues and radioresistance ovarian cancer cell lines. Transfection of miR-214 agomir in radiosensitive ovarian cancer cell lines promoted them for resistance to ionizing radiation, whereas transfection of miR-214 antagomir in radioresistance ovarian cancer cell lines sensitized them to ionizing radiation again. Furthermore, we found miR-214 effectively promoted tumor radioresistance in xenograft animal experiment. Western blotting and quantitative real-time PCR demonstrated that miR-214 negatively regulated PTEN in radioresistance ovarian cancer cell lines and ovarian cancer tissues. Taken together, our data conclude that miR-214 contributes to radioresistance of ovarian cancer by directly targeting PTEN.

scholarly journals The expression and function of toll-like receptors (TLRs) in ovarian cancer cell lines

2015 ◽  
Vol 3 (S2) ◽  
Author(s):  
Shin-Wha Lee ◽  
In-Kyung Lee ◽  
Sumin Kim ◽  
Sang-Eun Lee ◽  
Ha-Young Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Toll Like Receptors ◽  
Ovarian Cancer Cell Lines ◽  
And Function
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