ArticleOncogene2021
Inhibition of PFKFB3 induces cell death and synergistically enhances chemosensitivity in endometrial cancer.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Review
- First-in-Class Covalent Inhibitors of PFKFB3: Discovery and Characterization in PDAC Models.Journal of medicinal chemistry · 2026Article
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- PFKFB4 promotes M2 polarization of tumor-associated macrophages through aerobic glycolysis-mediated modification of histone H3K18 lactylation in hepatocellular carcinoma.Cancer & metabolism · 2026Article
- Mechanistic role of glycolytic pathways in the tumor microenvironment in driving chemoresistance.Frontiers in cell and developmental biology · 2026Review
- Enhanced glucose uptake promotes the survival of hepatocellular carcinoma cells following incomplete radiofrequency ablation.Molecular & cellular oncology · 2026Article
- Deciphering the Anti-Cancer Efficacy of the Combination of Small-Molecule Inhibitor KAN0438757 and Curcumin in Lung Cancer Cell Lines.Current issues in molecular biology · 2025Article
- Metabolic reprogramming and interventions in angiogenesis.Journal of advanced research · 2025Review
- Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.Cell communication and signaling : CCS · 2025Article
- Impact of glycolysis enzymes and metabolites in regulating DNA damage repair in tumorigenesis and therapy.Cell communication and signaling : CCS · 2025Review
- Molecular mechanisms and Biological Functions of Autophagy in Endometrial Diseases.International journal of medical sciences · 2025Review
- PFKFB3-dependent redox homeostasis and DNA repair support cell survival under EGFR-TKIs in non-small cell lung carcinoma.Cancer & metabolism · 2024Article
- Identification of PFKFB3 as a key factor in the development of colorectal cancer and immunotherapy resistance.Clinical and experimental medicine · 2024Article
- Sesamolin serves as an MYH14 inhibitor to sensitize endometrial cancer to chemotherapy and endocrine therapy via suppressing MYH9/GSK3β/β-catenin signaling.Cellular & molecular biology letters · 2024Article
- Multi-omics and immunogenomics analysis revealed PFKFB3 as a targetable hallmark and mediates sunitinib resistance in papillary renal cell carcinoma: in silico study with laboratory verification.European journal of medical research · 2024Article
- Focusing on the role of protein kinase mTOR in endometrial physiology and pathology: insights for therapeutic interventions.Molecular biology reports · 2024Review
- PFKFB3 deprivation attenuates the cisplatin resistance via blocking its autophagic elimination in colorectal cancer cells.Frontiers in pharmacology · 2024Article
- Glucose metabolism reprogramming in gynecologic malignant tumors.Journal of Cancer · 2024Review
- Advances in research on autophagy mechanisms in resistance to endometrial cancer treatment.Frontiers in oncology · 2024Review
- Oncometabolite lactate enhances breast cancer progression by orchestrating histone lactylation-dependent c-Myc expression.Translational oncology · 2023Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The advanced or recurrent endometrial cancer (EC) has a poor prognosis because of chemoresistance. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a glycolytic enzyme, is overexpressed in a variety of human cancers and plays important roles in promoting tumor cell growth. Here, we showed that high expression of PFKFB3 in EC cell lines is associated with chemoresistance. Pharmacological inhibition of PFKFB3 with PFK158 and or genetic downregulation of PFKFB3 dramatically suppressed cell proliferation and enhanced the sensitivity of EC cells to carboplatin (CBPt) and cisplatin (Cis). Moreover, PFKFB3 inhibition resulted in reduced glucose uptake, ATP production, and lactate release. Notably, we found that PFK158 with CBPt or Cis exerted strong synergistic antitumor activity in chemoresistant EC cell lines, HEC-1B and ARK-2 cells. We also found that the combination of PFK158 and CBPt/Cis induced apoptosis- and autophagy-mediated cell death through inhibition of the Akt/mTOR signaling pathway. Mechanistically, we found that PFK158 downregulated the CBPt/Cis-induced upregulation of RAD51 expression and enhanced CBPt/Cis-induced DNA damage as demonstrated by an increase in γ-H2AX levels in HEC-1B and ARK-2 cells, potentially revealing a means to enhance PFK158-induced chemosensitivity. More importantly, PFK158 treatment, either as monotherapy or in combination with CBPt, led to a marked reduction in tumor growth in two chemoresistant EC mouse xenograft models. These data suggest that PFKFB3 inhibition alone or in combination with standard chemotherapy may be used as a novel therapeutic strategy for improved therapeutic efficacy and outcomes of advanced and recurrent EC patients.
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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.