Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA110961 | ENA |
REPOSITORIES: ENA
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Project description:We found constitutive upregulation and higher degree induction of drug metabolism and disposition-related genes in a three-dimensional HepG2 culture. The upregulated genes are those believed to be regulated by different regulatory factors. The global gene expression analysis by Affymetrix GeneChip indicated that altered expressions of microtubule-related genes may change expressed levels of drug metabolism and disposition genes. Stabilization of the microtubule molecules with docetaxel, a tubulin stabilizing agent, in the two-dimensional culture showed gene expression patterns similar to those in the three-dimensional culture, indicating that culture environment affects drug metabolism functions in HepG2 cells. Keywords: radial flow bioreactor cell culture system, three dimensional culture, HepG2, GeneChip U133A,
2009-02-24 | GSE12939 | GEO
Project description:We found constitutive upregulation and higher degree induction of drug metabolism and disposition-related genes in a three-dimensional HepG2 culture. The upregulated genes are those believed to be regulated by different regulatory factors. The global gene expression analysis by Affymetrix GeneChip indicated that altered expressions of microtubule-related genes may change expressed levels of drug metabolism and disposition genes. Stabilization of the microtubule molecules with docetaxel, a tubulin stabilizing agent, in the two-dimensional culture showed gene expression patterns similar to those in the three-dimensional culture, indicating that culture environment affects drug metabolism functions in HepG2 cells. Experiment Overall Design: We compared the gene expression data from HepG2 cells cultured in the radial flow bioreactor (RFB) cell culture system for six days to those from HepG2 cells cultured in tissue culture plates for five days. Both cell cultures (RFB culture and plate culture) were performed twice independently. In each culture, three samples were collected from three different portions of the bioreactor or from three different tissue culture plates. Microarray analyses were performed in duplicate for each sample using the Affymetrix human genome U133A GeneChip.
2009-03-08 | E-GEOD-12939 | biostudies-arrayexpress
Project description:The development of more complex but reliable systems for compound testing in a pharmaceutical context is a challenging task to date. Three-dimensional (3D), organ mimetic cell culture is aiming to become an alternative to common two-dimensional (2D) cell culture or animal testing in that field. We developed a biocompatible 3D cell culture environment for a hepatocellular carcinoma (HCC) model that enables cellular maintenance in a polycarbonate scaffold structure. Albumin, regarded as a differentiation marker, was elevated in statically 3D cultivated HepG2 cells. Expression of HCC tumor marker alpha-fetoprotein (AFP) was reduced compared to immunofluorescence stainings of 2D cultivated cells. Remarkably, expression of cytokeratin and pathophysiologically relevant beta-1 integrin (ITGB1) was found enhanced in nonperfused 3D cell culture. Changes in gene expression induced by the 3D cultivation environment were investigated using Ingenuity Pathway Analysis (IPA). Our findings revealed involvement of the insulin growth factor (IGF) signaling pathway in upregulation of matrix metalloproteinases (MMP) and ITGB1. The experimental data indicate a more differentiated state in 3D cultivated HepG2 cells than in the respective 2D experiments. Hence, scaffold-supported 3D cultivation of HepG2 cells may lead to a gain of information valuable for both drug testing and cancer research. HepG2 cells were cultivated for five days under 2D and 3D statical and perfused conditions. Cultivation was started with 0.25x10^6 cells in 2D and with 1x10^6 vital cells for the 3D experiments. The day of seeding was defined as d0. The groups were classified as follows: 2D, i.e., monolayer cultures, 3D, i.e., statical 3D cultures and BR, which denotes perfused 3D culture of HepG2 cells. The perfusable bioreactor system was operated using a peristaltic pump. It houses the MatriGrid, a polycarbonate-based microporous cellular support. For 3D static cultivation, cell-inoculated MatriGrids were placed in wells of a 24-well plate. Microarray experiments of three 2D (i.e., control), three 3D statically and three actively perfused 3D cultivations were performed at SIRS-Lab GmbH (SIRS-Lab GmbH, Jena, Germany) according to the manufacturer's instructions (Illumina, San Diego, CA). Altogether, 9 RNA samples of hepatocyte cultures and an internal control RNA were hybridized on two HumanHT-12 v4 Expression BeadChips.
2012-11-01 | E-GEOD-41962 | biostudies-arrayexpress
Project description:The development of more complex but reliable systems for compound testing in a pharmaceutical context is a challenging task to date. Three-dimensional (3D), organ mimetic cell culture is aiming to become an alternative to common two-dimensional (2D) cell culture or animal testing in that field. We developed a biocompatible 3D cell culture environment for a hepatocellular carcinoma (HCC) model that enables cellular maintenance in a polycarbonate scaffold structure. Albumin, regarded as a differentiation marker, was elevated in statically 3D cultivated HepG2 cells. Expression of HCC tumor marker alpha-fetoprotein (AFP) was reduced compared to immunofluorescence stainings of 2D cultivated cells. Remarkably, expression of cytokeratin and pathophysiologically relevant beta-1 integrin (ITGB1) was found enhanced in nonperfused 3D cell culture. Changes in gene expression induced by the 3D cultivation environment were investigated using Ingenuity Pathway Analysis (IPA). Our findings revealed involvement of the insulin growth factor (IGF) signaling pathway in upregulation of matrix metalloproteinases (MMP) and ITGB1. The experimental data indicate a more differentiated state in 3D cultivated HepG2 cells than in the respective 2D experiments. Hence, scaffold-supported 3D cultivation of HepG2 cells may lead to a gain of information valuable for both drug testing and cancer research.
2012-11-01 | GSE41962 | GEO
Project description:Investigation of whole genome gene expression level changes in hepatocellular carcinoma cell line hepG2 in regular culture, hepG2-slug in regular culture and hepG2-slug on Matrigel. Whole genome gene expression level changes have been compared in hepatocellular carcinoma cell line hepG2 in regular culture, hepG2-slug in regular culture and hepG2-slug on Matrigel. Roche NimbleGen micro-array analysis was employed to assess global genome expression in HepG2 in regular culture, HepG2-slug in regular culture and HepG2-slug on Matrigel. The results demonstrated that the up-regulated genes and the down-regulated genes increased significantly when HepG2-slug cells with VM forming ablity were cultured on Matrigel and formed VM.
2012-09-21 | E-GEOD-41026 | biostudies-arrayexpress
Project description:High-Grade Serous Ovarian Carcinoma (HGSOC) is is the most common form of ovarian cancer and finding new treatments remains an unmet need. While drug discovery is typically performed in two-dimensional (2D) monolayers, three-dimensional (3D) culture systems better mimic in vivo conditions. However, a comprehensive comparison of 3D vs 2D ovarian cancer models is lacking. Here, we quantitatively compared the whole cell proteomic signatures of 4 ovarian cell lines—PEO1, PEO4, UWB1.289, and UWB1.289+BRCA1— with different status of BRCA genes grown, in 2D and in 3D. Using isobaric labeling proteomics, we quantified 6,668 proteins and identified 412 significantly altered proteins between 2D and 3D. Proteins upregulated in 3D were enriched for transmembrane transport and oxidoreductase activity, while energy metabolism and cell growth pathways also showed dimensionality-dependent changes. Notably, membrane-associated proteins such as EGFR were downregulated in spheroids, particularly in PEO1 and PEO4. Furthermore, 3D culture modulated the response to carboplatin, with increased expression of drug resistance-associated proteins, including NDUF family members and ATP6V0A2, in all spheroid models. These findings underscore how culture dimensionality influences both the molecular landscape and chemotherapeutic response of HGSOC cells and highlight candidate targets for overcoming carboplatin resistance.
2025-10-13 | PXD062934 | Pride
Project description:High-Grade Serous Ovarian Carcinoma (HGSOC) is the most common form of ovarian cancer and finding new treatments remains an unmet need. While drug discovery is typically performed in two-dimensional (2D) monolayers, three-dimensional (3D) culture systems better mimic in vivo conditions. However, a comprehensive comparison of 3D vs 2D ovarian cancer models is lacking. Here, we quantitatively compared the whole cell proteomic signatures of 4 ovarian cell lines—PEO1, PEO4, UWB1.289, and UWB1.289+BRCA1— with different status of BRCA genes grown, in 2D and in 3D. Using isobaric labeling proteomics, we quantified 6,404 proteins and identified 371 significantly and commonly altered proteins between 2D and 3D. Proteins upregulated in 3D were enriched for transmembrane transport and NADH:ubiquinone oxidoreductase Complex I, while energy metabolism and cell growth pathways also showed dimensionality-dependent changes. Notably, membrane-associated proteins were downregulated in spheroids, particularly EGFR in PEO1. Furthermore, 3D culture modulated the response to carboplatin, with increased expression of drug resistance-associated proteins, including NDUF family members in all spheroid models. These findings underscore how culture dimensionality influences both the molecular landscape and chemotherapeutic response of HGSOC cells and highlight candidate targets for overcoming carboplatin resistance.
2025-10-13 | PXD066652 | Pride
Project description:Preclinical cancer drug discovery efforts have employed two-dimensional (2D)-cell-based assay models, which fail to forecast in vivo efficacy and contribute to a lower success rates of clinical approval. Three-dimensional (3D) cell culture models are recently expected to bridge the gap between 2D and in vivo models. We have developed novel 3D culture method that improves the growth of spheroid-forming cancer cells under anchorage-independent condition by leveraging a feature of FP001. Gene microarrays were used to observe the global gene expression in A549 cells cultured in multi-well plate with or without FP001 and identified distinct classes of up or down-regulated genes.
2015-07-31 | GSE69577 | GEO
Project description:To further the development of an in vitro model that can more faithfully recapitulate drug disposition of orally administered drugs, we investigated the utility of human enteroid monolayers to simultaneously assess intestinal drug absorption and first-pass metabolism processes. We cultured human enteroid monolayers from three donors, derived via biopsies containing duodenal stem cells that were propagated and then differentiated atop permeable Transwell® inserts, and confirmed transformation into a largely enterocyte population via RNA-seq analysis and immunocytochemical (ICC) assays. Proper cell morphology was assessed and confirmed via bright field microscopy and ICC imaging of tight junction proteins and other apically and basolaterally localized proteins. Enteroid monolayer barrier integrity was demonstrated by elevated transepithelial electrical resistance (TEER) that stabilized after 10 days in culture and persisted for 42 days. These results were corroborated by low paracellular transport probe permeability at 7 and 21 days in culture. The activity of a prominent drug metabolizing enzyme, CYP3A, was confirmed at 7, 21, and 42 days culture under basal, 1?,25(OH)2 vitamin D3-induced, and 6',7'-dihydroxybergamottin-inhibited conditions. The duration of these experiments is particularly noteworthy, as this is the first study assessing DMET function for enteroids cultured for greater than 12 days. The sum of these results suggests enteroid monolayers are a promising in vitro model to investigate and quantitatively predict an orally administered drug's intestinal absorption and/or metabolism and associated drug-drug/natural product-drug interactions.
2025-01-17 | GSE253641 | GEO
Project description:Around 95% of anti-cancer drugs that show promise during preclinical study fail to gain FDA-approval for clinical use. This failure of the preclinical pipeline highlights the need for improved, physiologically-relevant in vitro models that can better serve as reliable drug-screening and disease modeling tools. The vascularized micro-tumor (VMT) is a novel three-dimensional model system (tumor-on-a-chip) that recapitulates the complex human tumor microenvironment, including perfused vasculature, within a transparent microfluidic device, allowing real-time study of drug responses and tumor–stromal interactions. Here we have validated this microphysiological system (MPS) platform for the study of colorectal cancer (CRC), the second leading cause of cancer-related deaths, by showing that gene expression, tumor heterogeneity, and treatment responses in the VMT more closely model CRC tumor clinicopathology than current standard drug screening modalities, including 2-dimensional monolayer culture and 3-dimensional spheroids.
2022-06-10 | GSE205641 | GEO