Comparison of 2D and 3D cell culture models for cell growth, gene expression and drug resistance

Fontoura, Julia Crispim da; Viezzer, Christian; Santos, Fabiana G. dos; Ligabue, Rosane Angélica; Weinlich, Ricardo; Puga, Renato D; Antonow, Dyeison; Severino, Patrícia; Bonorino, Cristina

doi:10.1016/j.msec.2019.110264

Cited by 234 publications

(168 citation statements)

References 44 publications

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“…Despite the promising effects that we observed in monolayer cultures, they were not detected in 3D cultures. It was expectable that in 3D the same drug concentrations did not induce the same degree of cytotoxicity than in monolayer, as 3D cultures seem more resistant to drugs cytotoxicity [ 151 , 152 ], including Dox in 3D BC models [ 153 , 154 ]. Our results support this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of Seaweed Compounds, Alone or Combined to Reference Drugs, against Breast Cell Lines Cultured in 2D and 3D

Malhão

Ramos

Macedo

et al. 2021

Toxics

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Seaweed bioactive compounds have shown anticancer activities in in vitro and in vivo studies. However, tests remain limited, with conflicting results, and effects in combination with anticancer drugs are even scarcer. Here, the cytotoxic effects of five seaweed compounds (astaxanthin, fucoidan, fucosterol, laminarin, and phloroglucinol) were tested alone and in combination with anticancer drugs (cisplatin—Cis; and doxorubicin—Dox), in breast cell lines (three breast cancer (BC) subtypes and one non-tumoral). The combinations revealed situations where seaweed compounds presented potentiation or inhibition of the drugs’ cytotoxicity, without a specific pattern, varying according to the cell line, concentration used for the combination, and drug. Fucosterol was the most promising compound, since: (i) it alone had the highest cytotoxicity at low concentrations against the BC lines without affecting the non-tumoral line; and (ii) in combination (at non-cytotoxic concentration), it potentiated Dox cytotoxicity in the triple-negative BC cell line. Using a comparative approach, monolayer versus 3D cultures, further investigation assessed effects on cell viability and proliferation, morphology, and immunocytochemistry targets. The cytotoxic and antiproliferative effects in monolayer were not observed in 3D, corroborating that cells in 3D culture are more resistant to treatments, and reinforcing the use of more complex models for drug screening and a multi-approach that should include histological and ICC analysis.

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Section: Discussionmentioning

confidence: 99%

Cytotoxicity of Seaweed Compounds, Alone or Combined to Reference Drugs, against Breast Cell Lines Cultured in 2D and 3D

Malhão

Ramos

Macedo

et al. 2021

Toxics

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“…Many mechanisms in tumor cells help in acquiring resistance to immune checkpoint blockade (ICB) therapy[19]. Previous studies have shown that cells grown in 3D models showed an increased resistance to I-O drugs as compared to 2D model[20; 21]. To evaluate this, we first compare the immune resistance feature of cancer cells in 2D vs. 3D tissueoids model.…”

Section: Resultsmentioning

confidence: 99%

AXTEX-4D™: A Novel 3Dex vivoplatform for preclinical investigations of immunotherapy agents

Baru

Sharma

Bpd

et al. 2020

Preprint

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The latest advancements in oncology are majorly focused on immuno-oncology (I-O) therapies. However, only ~7% of drugs are being approved from the preclinical discovery phase to phase 1. The most challenging issues in I-O is the problem of developing active and efficient drugs economically and on time. This mandates an urgent need for better preclinical screening models that closely mimic the in vivo tumor microenvironment. The established and most common methods for investigating the tumoricidal activity of I-O drugs are either two-dimensional (2D) systems or primary tumor cells in standard tissue culture vessels. However, they do not mimic the tumor microenvironment. Therefore, the more in vivo-like three-dimensional (3D) multicellular tumor spheroids are quickly becoming the favored model to examine immune cell-mediated responses in reaction to the administration of I-O drugs. Accordingly, we have demonstrated the utility of the three-dimensional ex vivo oncology model, developed on our novel AXTEX-4D™ platform to assess therapeutic efficacies of I-O drugs by investigating immune cell proliferation, migration, infiltration, cytokine profiling, and cytotoxicity of tumor tissueoids. The platform eliminates the need for additional biomolecules such as hydrogels and instead relies on the cancer cells themselves to create their own gradients and microenvironmental factors. In effect, the more comprehensive and in vivo like immune-oncology model developed on AXTEX-4D™ platform can be utilized for high-throughput screening of immunotherapeutic drugs.

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“…In addition, the combined treatment provides pronounced spheroid [32]. However, very few data are available about the gene expression differences between melanoma cells cultured as monolayer (2D) and spheroids (3D) [14]. No data were published yet about the gene expression differences between drug sensitive and resistant melanoma cells growing under different cell culture (2D and 3D) conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported specific, differently expressed genes involved in BRAF inhibitor resistance in melanoma cell lines, however most of these studies are based on monolayer cell cultures [ 32 ]. However, very few data are available about the gene expression differences between melanoma cells cultured as monolayer (2D) and spheroids (3D) [ 14 ]. No data were published yet about the gene expression differences between drug sensitive and resistant melanoma cells growing under different cell culture (2D and 3D) conditions.…”

Section: Discussionmentioning

confidence: 99%

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Gene Expression Signature of BRAF Inhibitor Resistant Melanoma Spheroids

Koroknai

Patel

Szász

et al. 2020

Pathol. Oncol. Res.

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In vitro cell cultures are frequently used to define the molecular background of drug resistance. The majority of currently available data have been obtained from 2D in vitro cultures, however, 3D cell culture systems (spheroids) are more likely to behave similarly to in vivo conditions. Our major aim was to compare the gene expression signature of 2D and 3D cultured BRAFV600E mutant melanoma cell lines. We successfully developed BRAF-drug resistant cell lines from paired primary/ metastatic melanoma cell lines in both 2D and 3D in vitro cultures. Using Affymetrix Human Gene 1.0 ST arrays, we determined the gene expression pattern of all cell lines. Our analysis revealed 1049 genes (562 upregulated and 487 downregulated) that were differentially expressed between drug-sensitive cells grown under different cell cultures. Pathway analysis showed that the differently expressed genes were mainly associated with the cell cycle, p53, and other cancer-related pathways. The number of upregulated genes (72 genes) was remarkably fewer when comparing the resistant adherent cells to cells that grow in 3D, and were associated with cell adhesion molecules and IGF1R signalling. Only 1% of the upregulated and 5.6% of the downregulated genes were commonly altered between the sensitive and the resistant spheroids. Interestingly, we found several genes (BNIP3, RING1 and ABHD4) with inverse expression signature between sensitive and resistant spheroids, which are involved in anoikis resistance and cell cycle regulation. In summary, our study highlights gene expression alterations that might help to understand the development of acquired resistance in melanoma cells in tumour tissue.

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Comparison of 2D and 3D cell culture models for cell growth, gene expression and drug resistance

Cited by 234 publications

References 44 publications

Cytotoxicity of Seaweed Compounds, Alone or Combined to Reference Drugs, against Breast Cell Lines Cultured in 2D and 3D

Cytotoxicity of Seaweed Compounds, Alone or Combined to Reference Drugs, against Breast Cell Lines Cultured in 2D and 3D

AXTEX-4D™: A Novel 3Dex vivoplatform for preclinical investigations of immunotherapy agents

Gene Expression Signature of BRAF Inhibitor Resistant Melanoma Spheroids

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