ArticleCancer management and research2020
Insulin Reduces the Efficacy of Vemurafenib and Trametinib in Melanoma Cells.
Article in Cancer management and research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Gender-specific associations of metabolic and circadian syndromes with melanoma risk: insights from NHANES 2007-2018.Scientific reports · 2025Article
- Mechanisms of Melanoma Progression and Treatment Resistance: Role of Cancer Stem-like Cells.Cancers · 2024Review
- A human-based multi-gene signature enables quantitative drug repurposing for metabolic disease.eLife · 2022Article
- Targeting Genome Stability in Melanoma-A New Approach to an Old Field.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite the progress made in the clinical management of metastatic melanoma, a patient's response to treatment cannot be fully predicted, and intrinsic or acquired resistance that is developed in most melanoma patients warrants further research efforts. In addition to genetic factors, microenvironmental input should be considered to explain the diversity of response to treatment among melanoma patients. In this study, we evaluated the impact of insulin on patient-derived BRAF
methodsCells were cultured in serum-free conditions, either with or without insulin. The activity of the MAPK/ERK and PI3K/AKT pathways was assessed by Western blotting, cell viability, and percentages of Ki-67- and NGFR-positive cells by flow cytometry. Transcript levels were analyzed using qRT-PCR, and γ-H2AX levels by immunoblotting and confocal microscopy. A luminescence-based assay was used to measure glutathione content.
resultsWhile insulin did not influence the MAPK/ERK pathway activity, it had a strong influence on melanoma cells, in which this pathway was suppressed by either vemurafenib or trametinib. In the presence of insulin, both drugs were much less efficient in 1) inhibiting proliferation and reducing the percentage of Ki-67-positive cells, and 2) inducing apoptosis and phosphorylation of histone H2AX in melanoma cells. Changes induced by vemurafenib and trametinib in glutathione homeostasis and DNA repair gene expression were also attenuated by insulin. Moreover, insulin impaired the combined effects of targeted drugs and doxorubicin in melanoma cells. In addition to insulin-induced PI3K/AKT activity, which was either transient or sustainable depending on the cell line, an insulin-triggered increase in the percentage of cells expressing NGFR, a marker of neural crest stem-like cells, may contribute to the reduced drug efficacy.
conclusionOur results demonstrate the role of insulin in reducing the efficacy of vemurafenib and trametinib. This needs clinical assessment.
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