ArticleLung cancer (Amsterdam, Netherlands)2018
Inhibition of IGF1R enhances 2-deoxyglucose in the treatment of non-small cell lung cancer.
Article in Lung cancer (Amsterdam, Netherlands), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- IGF1R Enhances Calcium Oxalate Monohydrate-Induced Epithelial-Mesenchymal Transition by Reprogramming Metabolism via the JAK2/STAT3 Signaling.International journal of biological sciences · 2025Article
- Construction of a novel lipid drop-mitochondria-associated genetic profile for predicting the survival and prognosis of lung adenocarcinoma.Discover oncology · 2024Article
- Identification and validation of a disulfidptosis-related genes prognostic signature in lung adenocarcinoma.Heliyon · 2024Article
- Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells.Open life sciences · 2024Article
- Metabolic reprogramming in lung cancer and its clinical implication.Frontiers in pharmacology · 2024Review
- The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- Novel mutation in hexokinase 2 confers resistance to 2-deoxyglucose by altering protein dynamics.PLoS computational biology · 2022Article
- Review
- Lymph node metastasis in lung squamous cell carcinoma and identification of metastasis-related genes based on the Cancer Genome Atlas.Cancer medicine · 2019Article
- MicroRNA-877 inhibits cell proliferation and invasion in non-small cell lung cancer by directly targeting IGF-1R.Experimental and therapeutic medicine · 2019Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveWe previously postulated that 2-deoxyglucose (2-DG) activates multiple pro-survival pathways through IGF1R to negate its inhibitory effect on glycolysis. Here, we evaluated whether IGF1R inhibitor synergizes with 2-DG to impede the growth of non-small cell lung cancer (NSCLC). MATERIALS AND
methodsThe activation of IGF1R signaling was assessed by the phosphorylation of IGF1R and its downstream target AKT using immunoblot. Drug dose response and combination index analyses were carried out according to the method of Chou and Talalay. Flow cytometry was used to evaluate cell cycle progression. Apoptosis was monitored by caspase-3/PARP cleavages or Annexin V staining. A subcutaneous xenograft model was used to assess this combination in vivo.
results2-DG induces the phosphorylation of IGF1R in its kinase domain, which can be abolished by the IGF1R inhibitor BMS-754807. Furthermore, the combination of 2-DG and BMS-754807 synergistically inhibited the survival of several non-small cell lung cancer (NSCLC) cell lines both in vitro and in vivo. The mechanistic basis of this synergy was cell line-dependent, and LKB1-inactivated EKVX cells underwent apoptosis following treatment with a subtoxic dose of 2-DG and BMS-754807. For these cells, the restoration of LKB1 kinase activity suppressed apoptosis induced by this combination but enhanced G1 arrest. In H460 cells, the addition of 2-DG did not enhance the low level of apoptosis induced by BMS-754807. However, treatment with 0.75 μM of BMS-754807 resulted in the accumulation of H460 cells with 8n-DNA content without affecting cell density increases. Hence, H460 cells may escape BMS-754807-induced G2/M cell cycle arrest through polyploidy. The inclusion of 2-DG blocked formation of the 8n-DNA cell population and restored G2/M phase cell cycle arrest.
conclusionThe combination of 2-DG and IGF1R inhibitor BMS-754807 may be used to suppress the proliferation of NSCLC tumors through different mechanisms.
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