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| Status |
Public on Jun 20, 2014 |
| Title |
Non-steroidal Anti-inflammatory Drugs Decrease E2F1 Expression and Inhibit Cell Growth in Ovarian Cancer Cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs) drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.
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| Overall design |
The serous ovarian adenocarcinoma cell lines HEY, OVCAR5 and UCI-101 were grown in culture then seeded in 60 mm dishes and treated for 24 hours with 300 mM diclofenac, indomethacin or no treatment (Control). RNA was isolated and one sample from each group was labeled and hybridized to Illumina Sentrix bead arrays.
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| Contributor(s) |
Valle BL, D’Souza T, Becker KG, Wood WH, Zhang Y, Wersto RP, Morin PJ |
| Citation(s) |
23637916 |
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| Submission date |
Mar 12, 2013 |
| Last update date |
Jun 22, 2020 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
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| Department |
Laboratory of Genetics and Genomics
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| Lab |
Computational Biology & Genomics Core
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| Street address |
251 Bayview Blvd
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL6104 |
Illumina humanRef-8 v2.0 expression beadchip |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA192899 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE45052_RAW.tar |
3.4 Mb |
(http)(custom) |
TAR |
| GSE45052_non-normalized.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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