ArticleBritish journal of pharmacology2014
Increased drug resistance is associated with reduced glucose levels and an enhanced glycolysis phenotype.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 83 citations in OpenAlex.
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- PIK3C2B drives lung cancer progression through coordinating metabolic reprogramming and EMT-mediated metastasis.Biochemistry and biophysics reports · 2025Article
- Natural anti-cancer products: insights from herbal medicine.Chinese medicine · 2025Review
- Disruption of DMD gene leads to altered calcium homeostasis and metabolic shift impacting gastric Cancer cell proliferation and migration.Cancer cell international · 2025Article
- Enhancing antitumor efficacy of CLDN18.2-directed antibody-drug conjugates through autophagy inhibition in gastric cancer.Cell death discovery · 2024Article
- Curcumin Inhibits the PPARδ-p-Akt-GLUT1 Pathway and Ameliorates the Antiproliferative Effects of Doxorubicin in MDA-MB-231 Cells.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- THADA inhibits autophagy and increases 5-FU sensitivity in gastric cancer cells via the PI3K/AKT/mTOR signaling pathway.Iranian journal of basic medical sciences · 2024Article
- The emerging role of glycolysis and immune evasion in gastric cancer.Cancer cell international · 2023Review
- A novel organic arsenic derivative MZ2 remodels metabolism and triggers mtROS-mediated apoptosis in acute myeloid leukemia.Journal of cancer research and clinical oncology · 2023Article
- Clinicopathological characteristics, molecular features and novel diagnostic strategies for the detection of malignant transformation of endometriosis (Review).Experimental and therapeutic medicine · 2023Review
- Article
- Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells.Journal of microbiology (Seoul, Korea) · 2022Article
- Harnessing Interactional Sensory Genes for Rationally Reprogramming Chaotic Metabolism.Research (Washington, D.C.) · 2022Article
- Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells.Open life sciences · 2022Article
- The history of small extracellular vesicles and their implication in cancer drug resistance.Frontiers in oncology · 2022Review
- CD147 Mediates 5-Fluorouracil Resistance in Colorectal Cancer by Reprogramming Glycolipid Metabolism.Frontiers in oncology · 2022Article
- NTheranostics · 2022Article
- The Emerging Roles of Circular RNAs in the Chemoresistance of Gastrointestinal Cancer.Frontiers in cell and developmental biology · 2022Review
- Everolimus regulates the activity of gemcitabine-resistant pancreatic cancer cells by targeting the Warburg effect via PI3K/AKT/mTOR signaling.Molecular medicine (Cambridge, Mass.) · 2021Article
- Effect of cell microenvironment on the drug sensitivity of hepatocellular cancer cells.Oncotarget · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe testing of anticancer compounds in vitro is usually performed in hyperglycaemic cell cultures, although many tumours and their in vivo microenvironments are hypoglycaemic. Here, we have assessed, in cultures of tumour cells, the effects of reduced glucose levels on resistance to anticancer drugs and investigated the underlying cellular mechanisms. EXPERIMENTAL APPROACH: PIK3CA mutant (AGS, HGC27), and wild-type (MKN45, NUGC4) gastric cancer cells were cultured in high-glucose (HG, 25 mM) or low-glucose (LG, 5 mM) media and tested for sensitivity to two cytotoxic compounds, 5-fluorouracil (5-FU) and carboplatin, the PI3K/mTOR inhibitor, PI103 and the mTOR inhibitor, Ku-0063794. KEY
resultsAll cells had increased resistance to 5-FU and carboplatin when cultured in LG compared with HG conditions despite having similar growth and cell cycle characteristics. On treatment with PI103 or Ku-0063794, only the PIK3CA mutant cells displayed increased resistance in LG conditions. The PIK3CA mutant LG cells had selectively increased p-mTOR, p-S6, p-4EBP1, GLUT1 and lactate production, and reduced reactive oxygen species, consistent with increased glycolysis. Combination analysis indicated PI103 and Ku-0063794 were synergistic in PIK3CA mutant LG cells only. Synergism was accompanied by reduced mTOR signalling and increased autophagy. CONCLUSIONS AND IMPLICATIONS: Hypoglycaemia increased resistance to cytotoxic agents, especially in tumour cells with a high dependence on glycolysis. Dual inhibition of the PI3K/mTOR pathway may be able to attenuate such hypoglycaemia-associated resistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.