Everolimus and plicamycin specifically target chemoresistant colorectal cancer cells of the CMS4 subtype

Jiayin Deng, Ai Ling Tian, Hui Pan, Allan Sauvat, Marion Leduc, Peng Liu, Liwei Zhao, Shuai Zhang, Hui Chen, Valérie Taly, Pierre Laurent-Puig, Laura Senovilla, Yingqiu Li, Guido Kroemer, Oliver Kepp

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    11 Citations (Scopus)

    Résumé

    Colorectal cancers (CRC) can be classified into four consensus molecular subtypes (CMS), among which CMS1 has the best prognosis, contrasting with CMS4 that has the worst outcome. CMS4 CRC is notoriously resistant against therapeutic interventions, as demonstrated by preclinical studies and retrospective clinical observations. Here, we report the finding that two clinically employed agents, everolimus (EVE) and plicamycin (PLI), efficiently target the prototypic CMS4 cell line MDST8. As compared to the prototypic CMS1 cell line LoVo, MDST8 cells treated with EVE or PLI demonstrated stronger cytostatic and cytotoxic effects, increased signs of apoptosis and autophagy, as well as a more pronounced inhibition of DNA-to-RNA transcription and RNA-to-protein translation. Moreover, nontoxic doses of EVE and PLI induced the shrinkage of MDST8 tumors in mice, yet had only minor tumor growth-reducing effects on LoVo tumors. Altogether, these results suggest that EVE and PLI should be evaluated for their clinical activity against CMS4 CRC.

    langue originaleAnglais
    Numéro d'article978
    journalCell Death and Disease
    Volume12
    Numéro de publication11
    Les DOIs
    étatPublié - 1 nov. 2021

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