Dataset Information

Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening.

ABSTRACT: Compared to various traditional 2D approaches, the scaffold-based 3D tumor models have emerged as an effective strategy to investigate the complex mechanisms behind cancer progression and responses to drug treatments, by providing biomimetic extracellular matrix and stromal-like microenvironments including the vascular elements. Herein, the development of a 3D endothelialized hepatic tumor microtissue model based on the fusion of multicellular aggregates of human hepatocellular carcinoma cells and human umbilical vein endothelial cells cocultured in poly(lactic-co-glycolic acid)-based porous microspheres (PLGA PMs) is reported. In contrast to the conventional 2D culture, the cells within the PLGA PMs exhibit significantly higher half-maximal inhibitory concentration values against anticancer drugs, including doxorubicin and cisplatin. Furthermore, the feasibility of coculturing other cell types, such as fibroblasts (L929) and HepG2 cells, is investigated. Together, the findings emphasize the significance of engineered 3D hepatic tumor microtissue models using PLGA PM-based multicellular aggregates for drug screening applications.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7610277 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening.

Wang Ying Y Kankala Ranjith Kumar RK Zhang Jianting J Hao Liuzhi L Zhu Kai K Wang Shibin S Zhang Yu Shrike YS Chen Aizheng A

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200921 21

Compared to various traditional 2D approaches, the scaffold-based 3D tumor models have emerged as an effective strategy to investigate the complex mechanisms behind cancer progression and responses to drug treatments, by providing biomimetic extracellular matrix and stromal-like microenvironments including the vascular elements. Herein, the development of a 3D endothelialized hepatic tumor microtissue model based on the fusion of multicellular aggregates of human hepatocellular carcinoma cells a ...[more]

PMID: 33173735

Similar Datasets

Project description:IntroductionSelenium (Se) is an essential trace element that exerts its effects mainly as the proteinogenic amino acid selenocysteine within a small set of selenoproteins. Among all family members, selenoprotein P (SELENOP) constitutes a particularly interesting protein as it serves as a biomarker and serum Se transporter from liver to privileged tissues. SELENOP expression is tightly regulated by dietary Se intake, inflammation, hypoxia and certain substances, but a systematic drug screening has hitherto not been performed.MethodsA compound library of 1861 FDA approved clinically relevant drugs was systematically screened for interfering effects on SELENOP expression in HepG2 cells using a validated ELISA method. Dilution experiments were conducted to characterize dose-responses. A most potent SELENOP inhibitor was further characterized by RNA-seq analysis to assess effect-associated biochemical pathways.ResultsApplying a 2-fold change threshold, 236 modulators of SELENOP expression were identified. All initial hits were replicated as biological triplicates and analyzed for effects on cell viability. A set of 38 drugs suppressed SELENOP expression more than three-fold, among which were cancer drugs, immunosuppressants, anti-infectious drugs, nutritional supplements and others. Considering a 90% cell viability threshold, resveratrol, vidofludimus, and antimony potassium-tartrate were the most potent substances with suppressive effects on extracellular SELENOP concentrations. Resveratrol suppressed SELENOP levels dose-dependently in a concentration range from 0.8 μM to 50.0 μM, without affecting cell viability, along with strong effects on key genes controlling metabolic pathways and vesicle trafficking.ConclusionThe results highlight an unexpected direct effect of the plant stilbenoid resveratrol, known for its antioxidative and health-promoting effects, on the central Se transport protein. The suppressive effects on SELENOP may increase liver Se levels and intracellular selenoprotein expression, thereby conferring additional protection to hepatocytes at the expense of systemic Se transport. Further physiological effects from this interaction require analyses in vivo and by clinical studies.

Dataset Information

Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening.

Publications

Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets