Disulfiram increases the efficacy of 5-fluorouracil in organotypic cultures of colorectal carcinoma
Jazyk angličtina Země Francie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
36076577
DOI
10.1016/j.biopha.2022.113465
PII: S0753-3322(22)00854-X
Knihovny.cz E-zdroje
- Klíčová slova
- 5-fluorouracil, Colorectal carcinoma, Disulfiram/copper, Organotypic culture, Spheroid, Synergism,
- MeSH
- buněčné sféroidy patologie MeSH
- disulfiram farmakologie MeSH
- fluoruracil * farmakologie terapeutické užití MeSH
- kolorektální nádory * farmakoterapie patologie MeSH
- lidé MeSH
- měď farmakologie terapeutické užití MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- disulfiram MeSH
- fluoruracil * MeSH
- měď MeSH
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 brightfield 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.
Department of Chemistry Faculty of Science Masaryk University Brno Czech Republic
Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic
International Clinical Research Center St Anne's University Hospital Brno Czech Republic
Citace poskytuje Crossref.org
