Surprising efficacy twist of two established cytostatics revealed by a-la-carte 3D cell spheroid preparation protocol

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F22%3A43924670" target="_blank" >RIV/60461373:22340/22:43924670 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0939641122002223?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0939641122002223?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejpb.2022.10.003" target="_blank" >10.1016/j.ejpb.2022.10.003</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Surprising efficacy twist of two established cytostatics revealed by a-la-carte 3D cell spheroid preparation protocol

Popis výsledku v původním jazyce

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, irinotecan affected the entire spheroid and caused its originally compact structure to disintegrate. The acquired results highlight the need to screen cancer chemotherapeutics on 3D tumor models, as contrasting results can be obtained compared to standard 2D cell cultures. © 2022 Elsevier B.V.

Název v anglickém jazyce

Surprising efficacy twist of two established cytostatics revealed by a-la-carte 3D cell spheroid preparation protocol

Popis výsledku anglicky

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, irinotecan affected the entire spheroid and caused its originally compact structure to disintegrate. The acquired results highlight the need to screen cancer chemotherapeutics on 3D tumor models, as contrasting results can be obtained compared to standard 2D cell cultures. © 2022 Elsevier B.V.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

20401 - Chemical engineering (plants, products)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Pharmaceutics and Biopharmaceutics

ISSN

0939-6411

e-ISSN

1873-3441

Svazek periodika

180

Číslo periodika v rámci svazku

NOV 2022

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

224-237

Kód UT WoS článku

000877551400003

EID výsledku v databázi Scopus

2-s2.0-85140066589