J 2022

Disulfiram increases the efficacy of 5-fluorouracil in organotypic cultures of colorectal carcinoma

HENDRYCH, Michal, Kamila ŘÍHOVÁ, Barbora ADAMOVÁ, Vojtěch HRADIL, Marek STIBOREK et. al.

Basic information

Original name

Disulfiram increases the efficacy of 5-fluorouracil in organotypic cultures of colorectal carcinoma

Authors

HENDRYCH, Michal (203 Czech Republic, belonging to the institution), Kamila ŘÍHOVÁ (203 Czech Republic, belonging to the institution), Barbora ADAMOVÁ (203 Czech Republic, belonging to the institution), Vojtěch HRADIL (203 Czech Republic, belonging to the institution), Marek STIBOREK (203 Czech Republic, belonging to the institution), Petr VLČEK (203 Czech Republic, belonging to the institution), Markéta HERMANOVÁ (203 Czech Republic, belonging to the institution), Jana VAŠÍČKOVÁ (203 Czech Republic), Petr BENEŠ (203 Czech Republic, belonging to the institution), Jan ŠMARDA (203 Czech Republic, belonging to the institution), Viktor KANICKÝ (203 Czech Republic, belonging to the institution), Jan PREISLER (203 Czech Republic, belonging to the institution) and Jarmila NAVRÁTILOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

BIOMEDICINE & PHARMACOTHERAPY, Paris, ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2022, 0753-3322

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

France

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 7.500

RIV identification code

RIV/00216224:14310/22:00127468

Organization unit

Faculty of Science

UT WoS

000878127600004

Keywords in English

Disulfiram/copper; 5-fluorouracil; Synergism; Organotypic culture; Spheroid; Colorectal carcinoma

Tags

International impact, Reviewed
Změněno: 28/2/2024 09:31, Mgr. Tereza Miškechová

Abstract

V originále

Drug efficacy determined in preclinical research is difficult to transfer to clinical practice. This is mainly due to the use of oversimplified models omitting the effect of the tumor microenvironment and the presence of various cell types participating in the formation of tumors in vivo. In this study, we used robust three-dimensional models including spheroids grown from colon cancer cell lines and organotypic cultures prepared from the colorectal carcinoma tissue to test novel therapeutic strategies. We developed a multi-modal approach combining bright-field and fluorescence microscopy for evaluating drug effects on organotypic cultures. Combined treatment with 5-fluorouracil and disulfiram/copper efficiently eliminated cancer cells in these 3D models. Moreover, disulfiram/copper down-regulated the expression of markers associated with 5-fluorouracil resistance, such as thymidylate synthase and CD133/CD44. Thus, we propose combined therapy of 5-fluorouracil and disulfiram/copper for further testing as a treatment for colorectal carcinoma. In addition, we show that organotypic cultures are suitable models for anti-cancer drug testing.

Links

GA18-16583S, research and development project
Name: Zobrazovací hmotnostní spektrometrie jednotlivých nanočástic
Investor: Czech Science Foundation
LX22NPO5102, research and development project
Name: Národní ústav pro výzkum rakoviny (Acronym: NÚVR)
Investor: Ministry of Education, Youth and Sports of the CR, National institute for cancer research, 5.1 EXCELES
MUNI/A/1325/2021, interní kód MU
Name: Podpora výzkumné činnosti studentů molekulární biologie a genetiky 10 (Acronym: MBG10)
Investor: Masaryk University
MUNI/A/1408/2021, interní kód MU
Name: Organotypické kultury glioblastomu – personalizované testování protinádorové léčby
Investor: Masaryk University

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