ArticleDrug design, development and therapy2014
Insulin induces drug resistance in melanoma through activation of the PI3K/Akt pathway.
Article in Drug design, development and therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- An Itch Receptor Drives Melanoma.bioRxiv : the preprint server for biology · 2026Article
- Life Factors and Melanoma: From the Macroscopic State to the Molecular Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Gender-specific associations of metabolic and circadian syndromes with melanoma risk: insights from NHANES 2007-2018.Scientific reports · 2025Article
- In Vivo PK-PD and Drug-Drug Interaction Study of Dorzagliatin for the Management of PI3Kα Inhibitor-Induced Hyperglycemia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Spatial transcriptomics analysis identifies a tumor-promoting function of the meningeal stroma in melanoma leptomeningeal disease.Cell reports. Medicine · 2024Article
- Mechanisms of Melanoma Progression and Treatment Resistance: Role of Cancer Stem-like Cells.Cancers · 2024Review
- A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer.Communications biology · 2024Article
- Spatial transcriptomics analysis identifies a unique tumor-promoting function of the meningeal stroma in melanoma leptomeningeal disease.bioRxiv : the preprint server for biology · 2023Article
- Bone marrow mesenchymal stem cell-derived exosomes reduce insulin resistance and obesity in mice via the PI3K/AKT signaling pathway.FEBS open bio · 2023Article
- Acacetin inhibits myocardial mitochondrial dysfunction by activating PI3K/AKT in SHR rats fed with fructose.Journal of natural medicines · 2023Article
- Isolation, Structural Characterization, and Hypoglycemic Activities In Vitro of Polysaccharides fromMolecules (Basel, Switzerland) · 2022Article
- The PIK3CA H1047R Mutation Confers Resistance to BRAF and MEK Inhibitors in A375 Melanoma Cells through the Cross-Activation of MAPK and PI3K-Akt Pathways.Pharmaceutics · 2022Article
- RSK2 promotes melanoma cell proliferation and vemurafenib resistanceFrontiers in pharmacology · 2022Article
- Article
- Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells.Frontiers in oncology · 2021Article
- Insulin Reduces the Efficacy of Vemurafenib and Trametinib in Melanoma Cells.Cancer management and research · 2020Article
- Contactin 1 modulates pegylated arginase resistance in small cell lung cancer through induction of epithelial-mesenchymal transition.Scientific reports · 2019Article
- miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A.Journal of experimental & clinical cancer research : CR · 2019Article
- The Mechanism of Phillyrin from the Leaves ofBioMed research international · 2019Article
- Downregulation of NEAT1 reverses the radioactive iodine resistance of papillary thyroid carcinoma cell via miR-101-3p/FN1/PI3K-AKT signaling pathway.Cell cycle (Georgetown, Tex.) · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThere is currently no curative treatment for melanoma once the disease spreads beyond the original site. Although activation of the PI3K/Akt pathway resulting from genetic mutations and epigenetic deregulation of its major regulators is known to cause resistance of melanoma to therapeutic agents, including the conventional chemotherapeutic drug dacarbazine and the Food and Drug Administration-approved mutant BRAF inhibitors vemurafenib and dabrafenib, the role of extracellular stimuli of the pathway, such as insulin, in drug resistance of melanoma remains less understood.
objectiveTo investigate the effect of insulin on the response of melanoma cells to dacarbazine, and in particular, the effect of insulin on the response of melanoma cells carrying the BRAF(V600E) mutation to mutant BRAF inhibitors. An additional aim was to define the role of the PI3K/Akt pathway in the insulin-triggered drug resistance.
methodsThe effect of insulin on cytotoxicity induced by dacarbazine or the mutant BRAF inhibitor PLX4720 was tested by pre-incubation of melanoma cells with insulin. Cytotoxicity was determined by the MTS assay. The role of the PI3K/Akt pathway in the insulin-triggered drug resistance was examined using the PI3K inhibitor LY294002 and the PI3K and mammalian target of rapamycin dual inhibitor BEZ-235. Activation of the PI3K/Akt pathway was monitored by Western blot analysis of phosphorylated levels of Akt.
resultsRecombinant insulin attenuated dacarbazine-induced cytotoxicity in both wild-type BRAF and BRAF(V600E) melanoma cells, whereas it also reduced killing of BRAF(V600E) melanoma cells by PLX4720. Nevertheless, the protective effect of insulin was abolished by the PI3K and mTOR dual inhibitor BEZ-235 or the PI3K inhibitor LY294002.
conclusionInsulin attenuates the therapeutic efficacy of dacarbazine and PLX4720 in melanoma cells, which is mediated by activation of the PI3K/Akt pathway and can be overcome by PI3K inhibitors.
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