Proteomics reveals that cell density could affect the efficacy of drug treatment

Xue, Zhichao; Zeng, Jiaming; Li, Yongshu; Meng, Bo; Gong, Xiaoyun; Zhao, Yang; Dai, Xinhua

doi:10.1016/j.bbrep.2022.101403

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…Cell confluency, defined as the measurement of cell density in a culture dish or flask that corresponds to the percentage of the surface area covered by adherent cells 1 , is one of the crucial factors that affects the characteristics of tumor cells in cell culture 2 . Increase in cell density intensifies intracellular interactions and influences cellular metabolism 3 and expression of genes and proteins 2 . Notably, it has been shown that cell confluence correlates with glucose uptake and lactate production in epithelial cells 3 and affects gene expression 4 , 5 .…”

Section: Background and Summarymentioning

confidence: 99%

Integrative transcriptomic and proteomic profiling of the effects of cell confluency on gene expression

Lobo,

Shcherbinina,

Westholm

et al. 2024

Sci Data

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In this study we examine the impact of cell confluency on gene expression. We focused on Argonaute (AGO) protein dynamics and associated gene and protein expression in HEK293, A375, and SHSY5Y cell lines. As a consequence of cell confluency, AGO2 protein translocates into the nucleus. Therefore, we generated transcriptomic data using RNA sequencing to compare gene expression in subconfluent versus confluent cells, which highlighted significant alterations in gene regulation patterns directly corresponding to changes in cell density. Our study also encompasses miRNA profiling data obtained through small RNA sequencing, revealing miRNA expressional changes dependent on cellular confluency, as well as cellular localization. Finally, we derived proteomic data from mass spectrometry analyses following AGO1-4 immunoprecipitation, providing a comprehensive view of AGO interactome in both nuclear and cytoplasmic compartments under varying confluency. These datasets offer a detailed exploration of the cellular and molecular dynamics, influenced by cell confluency, presenting a valuable resource for further research in cellular biology, particularly in understanding the basic mechanisms of cell density in cancer cells.

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Section: Background and Summarymentioning

confidence: 99%

Integrative transcriptomic and proteomic profiling of the effects of cell confluency on gene expression

Lobo,

Shcherbinina,

Westholm

et al. 2024

Sci Data

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“…Investigating the cell cycle is critical in comprehending the complex mechanisms that regulate cell growth and identifying specific drugs and therapeutic targets that are evolved in cell cycle for the treatment of diseases, which are essential for maintaining healthy tissues. [30] Prior to the zinc ion treatment in the 3D AS model, the cell cycle and apoptosis of HUVECs and SMCs under hyperlipidemic and inflammatory conditions were investigated separately (Figures S3 and S4, Supporting Information). In the ox-LDL/TNF-𝛼/IL-1𝛽-treated groups, the percentages of HUVECs in the G0G1-phase were increased from 48.16% to 57.74% and 38.98% to 44.42% in 2D-and 3D-cultured HUVECs, respectively, implying inhibited cell transition from the G0G1-phase to the Sphase and G2M-phase during the DNA synthesis process to some extent, which was consistent to previously reported data (Fig- ure S3, Supporting Information).…”

Section: Evaluation Of Zinc Ions At Various Concentrationsmentioning

confidence: 99%

Revealing the Role of Zinc Ions in Atherosclerosis Therapy via an Engineered Three‐Dimensional Pathological Model

2023

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An incomplete understanding of the cellular functions and underlying mechanisms of zinc ions released from zinc‐based stents in atherosclerosis (AS) therapy is one of the major obstacles to their clinical translation. The existing evaluation methodology using cell monolayers has limitations on accurate results due to the lack of vascular architectures and pathological features. Herein, the authors propose a 3D biomimetic AS model based on a multi‐layer vascular structure comprising endothelial cells and smooth muscle cells with hyperlipidemic surroundings and inflammatory stimulations as AS‐prone biochemical conditions to explore the biological functions of zinc ions in AS therapy. Concentration‐dependent biphasic effects of zinc ions on cell growth are observed both in cell monolayers and 3D AS models. Nevertheless, the cells within 3D AS model exhibit more accurate biological assessments of the zinc ions, as evidenced by augmented pathological features and significantly higher half‐maximal inhibitory concentration values against zinc ions. Based on such a developed 3D biomimetic AS model, the inhibitory effects on the deoxyribonucleic acid (DNA) synthesis, significantly influenced biological processes like cell motility, proliferation, and adhesion, and several potential bio‐targets of zinc ions of cells are revealed.

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Optimization of a human induced pluripotent stem cell-derived sensory neuron model for the in vitro evaluation of taxane-induced neurotoxicity

Cantor,

Shen,

Jiang

et al. 2024

Sci Rep

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Human induced pluripotent stem cell-derived sensory neuron (iPSC-dSN) models are a valuable resource for the study of neurotoxicity but are affected by poor replicability and reproducibility, often due to a lack of optimization. Here, we identify experimental factors related to culture conditions that substantially impact cellular drug response in vitro and determine optimal conditions for improved replicability and reproducibility. Treatment duration and cell seeding density were both found to be significant factors, while cell line differences also contributed to variation. A replicable dose–response in viability was demonstrated after 48-h exposure to docetaxel or paclitaxel. Additionally, a replicable dose-dependent reduction in neurite outgrowth was demonstrated, demonstrating the applicability of the model for the examination of additional phenotypes. Overall, we have established an optimized iPSC-dSN model for the study of taxane-induced neurotoxicity.

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Proteomics reveals that cell density could affect the efficacy of drug treatment

Cited by 3 publications

References 30 publications

Integrative transcriptomic and proteomic profiling of the effects of cell confluency on gene expression

Integrative transcriptomic and proteomic profiling of the effects of cell confluency on gene expression

Revealing the Role of Zinc Ions in Atherosclerosis Therapy via an Engineered Three‐Dimensional Pathological Model

Optimization of a human induced pluripotent stem cell-derived sensory neuron model for the in vitro evaluation of taxane-induced neurotoxicity

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