Determining lovastatin-induced differences in expression between statin sensitive and insensitive MM cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE15946 | GEO | 2009/11/24
SECONDARY ACCESSION(S): PRJNA117001
REPOSITORIES: GEO
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Project description:The goals of this study were to determine global differences in transcript expression and regulation between MM cells that are sensitive or insensitive to lovastatin-induced apoptosis. To this end, two sensitive (KMS11 and H929) and two insensitive (LP1 and SKMM1) MM cell lines treated with 20uM lovastatin or an ethanol vehicle control for 16 hours. mRNA was extracted and prepared for mRNA expression microarrays (HG-U133 Plus 2) in triplicate. Keywords: drug-response across cell-lines Four cell-lines, each treated with lovastatin or vehicle control, with three replicates per condition
2010-05-20 | E-GEOD-15946 | biostudies-arrayexpress
Project description:Determining lovastatin-induced differences in expression between statin sensitive and insensitive MM cells
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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 3-Deazaneplanocin A (DZNep), one of S-adenosylhomocysteine (AdoHcy) hydrolase inhibitors, has shown antitumor activities in a broad range of solid tumors and acute myeloid leukemia. Here, we examined its effects on multiple myeloma (MM) cells and found that, at 500 nM, it potently inhibited growth and induced apoptosis in 2 of 8 MM cell lines. RNA from un-treated and DZNep treated cells was profiled by Affymetrix HG-U133 Plus 2.0 microarray and genes with a significant change in gene expression were determined by significance analysis of microarray (SAM) testing. ALOX5 was the most down-regulated gene (5.8-fold) in sensitive cells and was expressed at low level in resistant cells. The results were corroborated by quantitative RT-PCR. Western-blot analysis indicated ALOX5 was highly expressed only in sensitive cell line H929 and greatly decreased upon DZNep treatment. Ectopic expression of ALOX5 reduced sensitivity to DZNep in H929 cells. Furthermore, down-regulation of ALOX5 by RNA interference could also induce apoptosis in H929. Gene expression analysis on MM patient dataset indicated ALOX5 expression was significantly higher in MM patients compared to normal plasma cells. We also found that Bcl-2 was overexpressed in DZNep insensitive cells, and cotreatment with DZNep and ABT-737, a Bcl-2 family inhibitor, synergistically inhibited growth and induced apoptosis of DZNep insensitive MM cells. Taken together, this study shows one of mechanisms of the DZNep efficacy on MM correlates with its ability to down-regulate the ALOX5 levels. In addition, DZNep insensitivity might be associated with overexpression of Bcl-2, and the combination of ABT-737 and DZNep could synergistically induced apoptosis. These results suggest that DZNep may be exploited therapeutically for a subset of MM.
2011-07-04 | GSE26921 | GEO
Project description:The 3-Deazaneplanocin A (DZNep), one of S-adenosylhomocysteine (AdoHcy) hydrolase inhibitors, has shown antitumor activities in a broad range of solid tumors and acute myeloid leukemia. Here, we examined its effects on multiple myeloma (MM) cells and found that, at 500 nM, it potently inhibited growth and induced apoptosis in 2 of 8 MM cell lines. RNA from un-treated and DZNep treated cells was profiled by Affymetrix HG-U133 Plus 2.0 microarray and genes with a significant change in gene expression were determined by significance analysis of microarray (SAM) testing. ALOX5 was the most down-regulated gene (5.8-fold) in sensitive cells and was expressed at low level in resistant cells. The results were corroborated by quantitative RT-PCR. Western-blot analysis indicated ALOX5 was highly expressed only in sensitive cell line H929 and greatly decreased upon DZNep treatment. Ectopic expression of ALOX5 reduced sensitivity to DZNep in H929 cells. Furthermore, down-regulation of ALOX5 by RNA interference could also induce apoptosis in H929. Gene expression analysis on MM patient dataset indicated ALOX5 expression was significantly higher in MM patients compared to normal plasma cells. We also found that Bcl-2 was overexpressed in DZNep insensitive cells, and cotreatment with DZNep and ABT-737, a Bcl-2 family inhibitor, synergistically inhibited growth and induced apoptosis of DZNep insensitive MM cells. Taken together, this study shows one of mechanisms of the DZNep efficacy on MM correlates with its ability to down-regulate the ALOX5 levels. In addition, DZNep insensitivity might be associated with overexpression of Bcl-2, and the combination of ABT-737 and DZNep could synergistically induced apoptosis. These results suggest that DZNep may be exploited therapeutically for a subset of MM. Cells were treated with 0.5 μmol/L DZNep for 48 h. Total RNA was extracted by using the Qiagen RNeasy Mini kit (Germany). Gene expression was performed using the GeneChip® Human Genome U133A Array (Affymetrix) following the manufacturer’s instructions. Data analysis was performed using GeneSpring software from Agilent Technologies.
2011-07-04 | E-GEOD-26921 | biostudies-arrayexpress
Project description:The spermatogonial stem cells (SSCs) niche is critical for SSC maintenance and the subsequent spermatogenesis. Numerous reproductive hazards impair the SSC niche, thereby result in aberrant SSC self-renewal and male infertility. However, promising agents targeting the impaired SSC niche to promote SSC self-renewal are still limited. Here, we screen out and assess the effects of Lovastatin on the self-renewal of mouse spermatogonial stem cells (mSSCs). Mechanistically, Lovastatin promotes the self-renewal of mSSCs and inhibits its inflammation and apoptosis through the regulation of isoprenoid intermediates. Likewise, other statins exhibit similar effects on SSC self-renewal. Remarkably, the treatment by Lovastatin could promote the self-renewal of mSSCs in the male gonadotoxicity model generated by busulfan injection. Noteworthy, we demonstrate that Lovastatin could significantly enhance the self-renewal of in vitro cultured primate SSCs. Collectively, our findings uncover that lovastatin could promote the self-renewal of both murine and primate SSCs and have implications for the treatment of certain male infertility using small compounds.
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Project description:C57BL/6 mice were fed ad libitum for the first 5 days of the experiments with high fat high cholesterol (HFC) diet only. The next 7 days of the experiments mice were continuously fed on a HFC diet and simultaneously vehicle (control group), fenofibrate (100 mg/kg) or lovastatin (30 mg/kg) were orally daily administered. At the end of the experiment (day 12) fenofibrate and lovastatin significantly decreased plasma LDL levels, while plasma cholesterol levels were significantly decreased by lovastatin only. Gene expression analysis of hyperlipidemic mouse liver revealed 391 significantly modulated genes when compared to standard diet fed mice. KEGG pathways related to modulated genes were identified and the most significant were biosynthesis of steroids, metabolism of xenobiotics by cytochrome P450 and linoleic acid metabolism. These pathways were modulated in a way, which increased the clearance of lipids and decreased endogenous synthesis of fatty acids and cholesterol. Additionally, genes involved in the regulation of detoxification pathways were significantly upregulated. The hepatic gene expression profiles of fenofibrate and lovastatin-treated HFC diet fed mice were compared to the vehicle-treated HFC diet fed mice. In the fenofibrate-treated group 124 genes and in the lovastatin-treated group 38 genes were significantly modulated. In the fenofibrate-treated group the top three significantly modulated pathways are fatty acid metabolism, propanoate metabolism and ascorbate and aldarate metabolism. While in the lovastatin-treated group the top three significantly modulated pathways are glycosphingolipid biosynthesis, tyrosine metabolism and metabolism of xenobiotics by cytochrome P450. Expert based classification revealed that both fenofibrate an lovastatin significantly down-regulated genes encoding sterol-C4-methyl oxidase like and 7-dehydrocholesterol reductase. Additionally, the regulation of cholesterol at the transcriptional level was also significantly augmented by fenofibrate and lovastatin, as judged by increased expression of -1 and decreased expression of INSIG-2. Keywords: Drug treatment
2007-02-15 | GSE6652 | GEO
Project description:We report high-throughput profiling of gene expression from human colon adenocarcinoma Caco-2 line. We profile mRNA in lovastatin-treated cells, and examine the effect of AHR ligands, SGA360 or SGA315. This study provides a framework for understanding transcriptional changes caused by SGA360 or SGA315 during upon lovastatin use.
2020-04-23 | GSE130234 | GEO
Project description:C57BL/6 mice were fed ad libitum for the first 5 days of the experiments with high fat high cholesterol (HFC) diet only. The next 7 days of the experiments mice were continuously fed on a HFC diet and simultaneously vehicle (control group), fenofibrate (100 mg/kg) or lovastatin (30 mg/kg) were orally daily administered. At the end of the experiment (day 12) fenofibrate and lovastatin significantly decreased plasma LDL levels, while plasma cholesterol levels were significantly decreased by lovastatin only. Gene expression analysis of hyperlipidemic mouse liver revealed 391 significantly modulated genes when compared to standard diet fed mice. KEGG pathways related to modulated genes were identified and the most significant were biosynthesis of steroids, metabolism of xenobiotics by cytochrome P450 and linoleic acid metabolism. These pathways were modulated in a way, which increased the clearance of lipids and decreased endogenous synthesis of fatty acids and cholesterol. Additionally, genes involved in the regulation of detoxification pathways were significantly upregulated. The hepatic gene expression profiles of fenofibrate and lovastatin-treated HFC diet fed mice were compared to the vehicle-treated HFC diet fed mice. In the fenofibrate-treated group 124 genes and in the lovastatin-treated group 38 genes were significantly modulated. In the fenofibrate-treated group the top three significantly modulated pathways are fatty acid metabolism, propanoate metabolism and ascorbate and aldarate metabolism. While in the lovastatin-treated group the top three significantly modulated pathways are glycosphingolipid biosynthesis, tyrosine metabolism and metabolism of xenobiotics by cytochrome P450. Expert based classification revealed that both fenofibrate an lovastatin significantly down-regulated genes encoding sterol-C4-methyl oxidase like and 7-dehydrocholesterol reductase. Additionally, the regulation of cholesterol at the transcriptional level was also significantly augmented by fenofibrate and lovastatin, as judged by increased expression of -1 and decreased expression of INSIG-2. Experiment Overall Design: 24 seven week old mice were randomly divided in four experimental groups. Control group (n = 6) was fed on a standard chow diet (diet 3430, Provimi Kliba AG, Kaiseraugst, Switzerland) and treated orally once daily with vehicle for 12 days. Remaining 18 mice were fed on HFC diet for 12 days. On day five HFC diet fed mice were treated orally once daily either with vehicle (HFC group, n=6), lovastatin (HFC lovastatin group, 30mg/kg, n=6) or fenofibrate (HFC fenofibrate group, 100mg/kg, n=6). Doses of lovastatin and fenofibrate were choosen according to the literature review. On day 12 liver were excised and immediately frozen in liquid nitrogen and stored at -80°C for the subsequent transriptome analyses
2008-06-15 | E-GEOD-6652 | biostudies-arrayexpress