Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models
| Autor: | Tristan Rupp, Solène Debasly, Laurie Genest, Guillaume Froget, Vincent Castagné |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Lung Neoplasms
Fingolimod Hydrochloride Dimethyl Fumarate Organic Chemistry General Medicine Catalysis Computer Science Applications Inorganic Chemistry Mice Carcinoma Non-Small-Cell Lung Tumor Microenvironment Animals Humans Physical and Theoretical Chemistry non-small cell lung cancer preclinical models tumor progression Fingolimod dimethyl fumarate Molecular Biology Immunosuppressive Agents Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 15; Pages: 8192 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23158192 |
| Popis: | New therapies are required for patients with non-small cell lung cancer (NSCLC) for which the current standards of care poorly affect the patient prognosis of this aggressive cancer subtype. In this preclinical study, we aim to investigate the efficacy of Fingolimod, a described inhibitor of sphingosine-1-phosphate (S1P)/S1P receptors axis, and Dimethyl Fumarate (DMF), a methyl ester of fumaric acid, both already approved as immunomodulators in auto-immune diseases with additional expected anti-cancer effects. The impact of both drugs was analyzed with in vitro cell survival analysis and in vivo graft models using mouse and human NSCLC cells implanted in immunocompetent or immunodeficient mice, respectively. We demonstrated that Fingolimod and DMF repressed tumor progression without apparent adverse effects in vivo in three preclinical mouse NSCLC models. In vitro, Fingolimod did not affect either the tumor proliferation or the cytotoxicity, although DMF reduced tumor cell proliferation. These results suggest that Fingolimod and DMF affected tumor progression through different cellular mechanisms within the tumor microenvironment. Fingolimod and DMF might uncover potential therapeutic opportunities in NSCLC. |
| Databáze: | OpenAIRE |
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