A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay

Zhang, Wen; Liao, Quan; Hu, Ya; Li, You; Zhou, Lyu; Zhao, Yu

doi:10.1590/1414-431x20132647

Cited by 78 publications

(68 citation statements)

References 35 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Specifically, Wen et al [14] reported that 3D cultures (in Matrigel) of MIAPaCa-2 and PANC-1 pancreatic cancer cell lines, when treated with gemcitabine and 5-FU, had a higher resistance to the effects of these drugs in comparison to cells grown in 2D. Similarly, Ponce de León et al .…”

Section: Discussionmentioning

confidence: 99%

The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance

2016

View full text Add to dashboard Cite

Solid tumours naturally grow in 3D wherein the spatial arrangement of cells affects how they interact with each other. This suggests that 3D cell culture may mimic the natural in vivo setting better than traditional monolayer (2D) cell culture, where cells are grown attached to plastic. Here, using HER2-positive breast cancer cell lines as models (BT474, HCC1954, EFM192A), the effects of culturing cells in 3D using the poly-HEMA method compared to 2D cultures were assessed in terms of cellular viability, response/resistance to anti-cancer drugs, protein expression and enzyme activity. Scanning electron microscopy showed the morphology of cells in 3D to be substantially different to those cultured in 2D. Cell viability in 3D cells was substantially lower than that of cells in 2D cultures, while 3D cultures were more resistant to the effects of HER-targeted (neratinib) and classical chemotherapy (docetaxel) drugs. Expression of proteins involved in cell survival, transporters associated with drug resistance and drug targets were increased in 3D cultures. Finally, activity of drug metabolising enzyme CYP3A4 was substantially increased in 3D compared to 2D cultures. Together this data indicates that the biological information represented by 3D and 2D cell cultures is substantially different i.e. 3D cell cultures demonstrate higher innate resistance to anti-cancer drugs compared to 2D cultures, which may be facilitated by the altered receptor proteins, drug transporters and metabolising enzyme activity. This highlights the importance of considering 3D in addition to 2D culture methods in pre-clinical studies of both newer targeted and more traditional anti-cancer drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance

2016

View full text Add to dashboard Cite

show abstract

“…The main optimizations, practical, and troubleshooting approaches described in the literature for this technique will be overviewed hereafter (Figure 2). 2-Methoxyestradiol Glioblastoma U87MG [20] 5-Fluorouracil Pancreatic cancer MIAPaCa-2 [94] Panc-1 [94] Mercaptopurine (6-MP and 6-MPR)…”

Section: Optimization Of the Methodsology Used To Form 3d Spheroids Thmentioning

confidence: 99%

Spheroids Formation on Non‐Adhesive Surfaces by Liquid Overlay Technique: Considerations and Practical Approaches

Costa

Melo‐Diogo

Moreira

et al. 2017

Biotechnology Journal

130

125

View full text Add to dashboard Cite

Scalable and reproducible production of 3D cellular spheroids is highly demanded, by pharmaceutical companies, for drug screening purposes during the pre-clinical evaluation phase. These 3D cellular constructs, unlike the monolayer culture of cells, can mimic different features of human tissues, including cellular organization, cell-cell and cell-extracellular matrix (ECM) interactions. Up to now, different techniques (scaffold-based and -free) have been used for spheroids formation, being the Liquid Overlay Technique (LOT) one of the most explored methodologies, due to its low cost and easy handling. Additionally, during the last few decades, this technique has been widely investigated in order to enhance its potential for being applied in high-throughput analysis. Herein, an overview of the LOT advances, practical approaches, and troubleshooting is provided for those researchers that intend to produce spheroids using LOT, for drug screening purposes. Moreover, the advantages of the LOT over the other scaffold-free techniques used for the spheroids formation are also addressed. Highlights • 2D cell culture drawbacks are summarized;• spheroids mimic the features of human tissues;• scaffold-based and scaffold-free technologies for spheroids production are discussed; • advantages of LOT over other scaffold-free techniques are highlighted; • LOT advances, practical approaches and troubleshooting are underlined.

show abstract

“…Active cell proliferation is sometimes required for some drugs to be effective. 63 Examples of drugs that require active proliferation to be effective are 5-fluorouracil (5-FU) and doxorubicin. Tung et al 64 showed that the lack proliferating cells in A431.H9 3D…”

Section: Cell Cultures In Drug Discoverymentioning

confidence: 99%

Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors

Edmondson

Broglie

Adcock

et al. 2014

ASSAY and Drug Development Technologies

1,879

1,640

View full text Add to dashboard Cite

Three-dimensional (3D) cell culture systems have gained increasing interest in drug discovery and tissue engineering due to their evident advantages in providing more physiologically relevant information and more predictive data for in vivo tests. In this review, we discuss the characteristics of 3D cell culture systems in comparison to the two-dimensional (2D) monolayer culture, focusing on cell growth conditions, cell proliferation, population, and gene and protein expression profiles. The innovations and development in 3D culture systems for drug discovery over the past 5 years are also reviewed in the article, emphasizing the cellular response to different classes of anticancer drugs, focusing particularly on similarities and differences between 3D and 2D models across the field. The progression and advancement in the application of 3D cell cultures in cell-based biosensors is another focal point of this review.

show abstract

A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay

Cited by 78 publications

References 35 publications

The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance

The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance

Spheroids Formation on Non‐Adhesive Surfaces by Liquid Overlay Technique: Considerations and Practical Approaches

Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors

Contact Info

Product

Resources

About