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Surprising efficacy twist of two established cytostatics revealed by a-la-carte 3D cell spheroid preparation protocol by Jiřina Kroupová; Jaroslav Hanuš; František Štěpánek is a Pharmacology, Toxicology and Pharmaceutics article available to read on EtoBox.

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Three-dimensional cell culture systems are increasingly used for biological and anticancer drug screening as they mimic the structure and microenvironment of tumors more closely than conventional two-dimensional cell models. In this study, the growth kinetics of colon adenocarcinoma-derived spheroids (HT-29 cell line) cultivated in liquid marble micro-bioreactors and nonadherent PDMS-coated well plates was investigated in detail and enabled precise control of the spheroid size by the seed cell density and cultivation time. The therapeutic effect of 5-fluorouracil and irinotecan hydrochloride in 2D monolayer cell culture and 3D tumor spheroids revealed an unexpected twist in their efficacy due to different ability to penetrate through 3D microtissue. For 5-fluorouracil, the inhibitory concentration IC50 after 48 h exposure increased from 11.3 μM for a 2D cell culture to 707.7 μM for a 3D spheroid. In the case of irinotecan, IC50 increased from 24.9 μM to 77.8 μM. Despite its higher molar weight, irinotecan appeared to penetrate the 3D spheroid structure more efficiently than 5-fluorouracil. While 5-fluorouracil mainly caused a suppression of spheroid growth from the outside, irinote

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Author

Jiřina Kroupová; Jaroslav Hanuš; František Štěpánek

Publisher

Elsevier BV

Published

2022

Language

EN

Field

Pharmacology, Toxicology and Pharmaceutics (Life Sciences)