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

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Authors

HENDRYCH Michal ŘÍHOVÁ Kamila ADAMOVÁ Barbora HRADIL Vojtěch STIBOREK Marek VLČEK Petr HERMANOVÁ Markéta VAŠÍČKOVÁ Jana BENEŠ Petr ŠMARDA Jan KANICKÝ Viktor PREISLER Jan NAVRÁTILOVÁ Jarmila

Year of publication 2022
Type Article in Periodical
Magazine / Source BIOMEDICINE & PHARMACOTHERAPY
MU Faculty or unit

Faculty of Science

Citation
Web https://www.sciencedirect.com/science/article/pii/S075333222200854X?via%3Dihub
Doi http://dx.doi.org/10.1016/j.biopha.2022.113465
Keywords Disulfiram/copper; 5-fluorouracil; Synergism; Organotypic culture; Spheroid; Colorectal carcinoma
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Description 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.
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