Fluvastatin-induced differential global gene expression in human metastatic MDA-MB-231 breast cancer cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE59007 | GEO | 2014/09/01
SECONDARY ACCESSION(S): PRJNA254099
REPOSITORIES: GEO
Similar Datasets
Project description:The current study analyzed the altered expression profiles of genes that are responsible for fluvastatin-induced breast cancer cell death in MDA-MB-231 cells (ER-ve basal breast cancer cells). Some of these altered gene expressions were further inter connceted to various pathways which may eventually be recognised as drug targets/ biomarkers in statin-sensitve breast cancer patients. To understand the differential gene expression profile in fluvastatin treated (24 h) malignant breast cancer cells with untreated malignant breast cancer cells.
2014-09-01 | E-GEOD-59007 | biostudies-arrayexpress
Project description:The current study analyzed the altered expression profiles of genes that are responsible for fluvastatin-induced breast cancer cell death in MCF-7 cells (ER+ve luminal breast cancer cells). Some of these altered gene expressions were further inter connceted to various pathways which may eventually be recognised as drug targets/ biomarkers in statin-sensitve breast cancer patients.
2014-09-01 | GSE59006 | GEO
Project description:The current study analyzed the altered expression profiles of genes that are responsible for fluvastatin-induced breast cancer cell death in MCF-7 cells (ER+ve luminal breast cancer cells). Some of these altered gene expressions were further inter connceted to various pathways which may eventually be recognised as drug targets/ biomarkers in statin-sensitve breast cancer patients. To understand the differential gene expression profile in fluvastatin treated (24 h) malignant breast cancer cells with untreated malignant breast cancer cells.
2014-09-01 | E-GEOD-59006 | biostudies-arrayexpress
Project description:Background: Cholesterol pathway inhibition by statins prevents breast cancer development in mouse models of breast cancer but their efficacy is not very high (about 50%) . Therefore, the goal of this study is to investigate if the fluvastatin mediated upregulation in the steroid biosynthesis pathway genes limit the efficacy of statin chemoprevention. Methods: A published gene signature of statin resistance was validated in cell line-based models of inherent and acquired resistance during breast cancer. These signatures were next validated in a mouse model of hormone receptor negative breast cancer. Results: We found more than 70% of a published multi-gene fluvastatin resistance signature to be significantly upregulated in an inherently resistant cell line relative to fluvastatin sensitive cell line. We found this inherent statin resistance gene signature to be also shared with the signature of acquired resistance to fluvastatin (13 / 23 total genes). These 13 inherent resistance genes and 10 additional genes mapped to 2 of the top 3 deregulated pathways that are steroid-, and terpenoid backbone- biosynthesis pathway. Next, we tested if one or multiple genes of statin resistance signature, could predict efficacy of statin chemoprevention in the SV40 C3TAg transgenic mouse model. We found upregulation of a large number (19/24) of genes in the tumor bearing mammary glands, suggesting that upregulation of these pathways drives resistance to statin chemoprevention. A subset of 13-genes from this panel was significantly associated with response to statin treatment, as was the expression level of HMGCR alone in a mouse model of breast cancer. Lastly, we studied if a 10-day period of fluvastatin treatment to SV40C3 TAg mice, can also trigger the upregulation of these genes and provide an early signal of statin resistance. These experiments showed that a 10-day period is insufficient to cause a feedback upregulation in steroid biosynthesis pathway genes and thus cannot be used as an early biomarker to detect resistance to fluvastatin. Conclusions: High basal or restorative upregulation in the steroid biosynthesis pathway gene expression after fluvastatin treatment appears to be strongly associated with resistance to statin chemoprevention for breast cancer and may serve as a biomarker to identify patients that are most likely to respond to statins or develop resistance.
2022-03-01 | GSE174673 | GEO
Project description:Clinical data of patients suffering from COVID-19 have indicated that statin therapy, used to treat hypercholesterolemia, is associated with a better clinical outcome. We therefore investigated the effect of statins on SARS-CoV-2 infection in human lung cells and found that fluvastatin inhibited coronavirus infection, while other tested statins did not. Fluvastatin inhibited high and low pathogenic coronaviruses in vitro and ex vivo in a dose-dependent manner. Proteomic analyses of infected versus uninfected lung epithelial cells treated with fluvastatin, simvastatin, or rosuvastatin revealed that all tested statins modulated the cholesterol synthesis pathways without compromising the innate antiviral immune response. Strikingly, fluvastatin treatment uniquely affected the proteome of SARS CoV 2 infected cells, specifically downregulating proteins that modulate protein translation and viral replication. These results suggest that statin therapy poses no additional risk to individuals exposed to SARS-CoV-2 and that fluvastatin may have a moderate beneficial effect on SARS CoV-2 infection by modulating protein translation.
2021-12-07 | PXD023422 | Pride
Project description:The present gene expression array study of fluvastatin effects on monocytes from SLE patients show that fluvastatin has a global anti-inflammatory effect on monocytes, which includes attenuated expression of several proinflammatory cytokines, and regulated expression of molecules mediating lipoprotein signaling and cholesterol metabolism, as well as atherosclerosis and inflammatory signaling.
2014-03-12 | GSE45422 | GEO
Project description:Fluvastatin has been identified as novel inhibitors of metastasis in pancreatic cancer. In multiple in vivo and in vitro experiments the compounds phenotypic effects was validated. Since under drug treatment the transcriptomic changes in examined cell lines were rather small, we expected the underlying mechanistic effect to be on the level of the proteome and more importantly the phospho-proteome. To evaluate this assumption we performed label-free full proteome and phosphoproteomics experiments on Fluvastatin treated ASPC1 cells.
2021-11-29 | PXD022345 | Pride
Project description:The goal of this study was to determine the gene expression changes following fluvastatin treatment in t(4;14)-positive multiple myeloma (MM) cell lines. To this end, two cell lines (KMS11 and NCI-H929) were treated with fluvastatin (2 micromolar) or ethanol as a solvent control for 24 hours. RNA was extracted and prepared for high-throughput sequencing in duplicate.
2020-07-08 | GSE152327 | GEO
Project description:The present gene expression array study of fluvastatin effects on monocytes from SLE patients show that fluvastatin has a global anti-inflammatory effect on monocytes, which includes attenuated expression of several proinflammatory cytokines, and regulated expression of molecules mediating lipoprotein signaling and cholesterol metabolism, as well as atherosclerosis and inflammatory signaling. Twenty seven SLE patients were given 20mg/day fluvastatin for one month. Blood samples were obtained before the starting of the treatment and at the end of treatment. Total RNA from monocytes was extracted using TRIzol reagent. RNA quality control was performed in a 2100 Bioanalyzer. Complementary RNAs from six SLE patients (four before treatment and two after treatment) were prepared for hybridization in an Agilent G4112F platform (Whole human Genome microarray 44K) using the One-color gene expression system (Agilent technologies).
2014-03-12 | E-GEOD-45422 | biostudies-arrayexpress
Project description:Statins and bisphosponates (BPs) are two distinct classes of isoprenoid pathway inhibitors targeting HMG-CoA reductase (upstream enzyme) and Farnesyl-pyrophospate synthase (downstream enzyme) respectively. Here we conducted a comparative study of two representatives of these classes, fluvastatin (Fluva) and Zoledronate (Zol), to assess the differences in their in vivo metastatic potentials and pharmacogenomic profiles. Both drugs, being administered after emergence of detectable metastases, appeared to be potent metastasis inhibitors in MDA-MB-231 breast cancer metastasis model. We observed a reduced number of metastatic sites under Fluva, but not Zol treatment. Combinatorial in vivo treatment by Fluva and Zol showed no synergy for these drugs, as reported earlier on the basis of in vitro studies (Budman DR, Oncology 2006), staying in line with similarity of their transcriptomic profiles. Comparison of Zol and Fluva transcriptomic profiles revealed similar patterns of affected genes (describe involved genes functions) through different kinetics (when treated with IC50 determined for 72h treatment, the majority of changes were observed after 24h incubation with Fluva , and only after 48h incubation with Zol at 72h-IC50 or after 24h treatment with its 3 times higher dose). We demonstrated here that targeting different enzymes of the same pathway neither necessarily leads to distinct changes in gene profiles, nor to synergy for in vivo anti-metastatic potential.
2012-01-01 | GSE33552 | GEO