ArticleCancer science2019
Apatinib induces 3-hydroxybutyric acid production in the liver of mice by peroxisome proliferator-activated receptor α activation to aid its antitumor effect.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- A Phase II Clinical Study on Apatinib Plus Vinorelbine in Refractory HER2-Negative Breast Cancer and its Metabolic Implications of Drug Resistance.Current cancer drug targets · 2025Trial
- β-Hydroxybutyrate Inhibits Angiogenesis, Suppresses Non-Small Cell Lung Cancer Growth, and Enhances Gemcitabine Antitumor Activity.International journal of molecular sciences · 2026Article
- Efficacy and safety of apatinib versus sorafenib/placebo in first-line treatment for intermediate and advanced primary liver cancer: A systematic review and meta-analysis.Frontiers in pharmacology · 2023Review
- The Effect ofBioMed research international · 2023Article
- HMGCS2 Mediation of Ketone Levels Affects Sorafenib Treatment Efficacy in Liver Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Efficacy and safety of apatinib as second or later-line therapy in extensive-stage small cell lung cancer: a prospective, exploratory, single-arm, multi-center clinical trial.Translational lung cancer research · 2022Article
- The Protective Effects of Ganoderic Acids fromFoods (Basel, Switzerland) · 2022Article
- Research on the Mechanism and Prevention of Hypertension Caused by Apatinib Through the RhoA/ROCK Signaling Pathway in a Mouse Model of Gastric Cancer.Frontiers in cardiovascular medicine · 2022Article
- The impact of hyperglycaemic crisis episodes on long-term outcomes for inpatients presenting with acute organ injury: A prospective, multicentre follow-up study.Frontiers in endocrinology · 2022Article
- On the nutritional and therapeutic effects of ketone body D-β-hydroxybutyrate.Applied microbiology and biotechnology · 2021Review
- The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma.Cancers · 2021Review
- Apatinib-Induced Hand-Foot Skin Reaction in Chinese Patients With Liver Cancer.Frontiers in oncology · 2021Review
- Guhong Injection Protects Against Apoptosis in Cerebral Ischemia by Maintaining Cerebral Microvasculature and Mitochondrial Integrity Through the PI3K/AKT Pathway.Frontiers in pharmacology · 2021Article
- Serum Metabolomic Profiling to Reveal Potential Biomarkers for the Diagnosis of Fatty Liver Hemorrhagic Syndrome in Laying Hens.Frontiers in physiology · 2021Article
- Fenofibrate Exerts Antitumor Effects in Colon Cancer via Regulation of DNMT1 and CDKN2A.PPAR research · 2021Article
- Apatinib as an alternative therapy for advanced hepatocellular carcinoma.World journal of hepatology · 2020Review
- Apatinib induces 3-hydroxybutyric acid production in the liver of mice by peroxisome proliferator-activated receptor α activation to aid its antitumor effect.Cancer science · 2019Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Apatinib, an antiangiogenic agent, shows efficient antitumor activity in a broad range of malignancies. Considering tumor is a type of metabolic disease, we investigated the metabolomics changes in serum and tumor after apatinib treatment and the molecular mechanism of characteristic changes associated with its antitumor efficacy. Molecules in serum and tumor tissue were extracted and analyzed by a gas chromatography-mass spectrometry metabolic platform. Apatinib significantly inhibited e tumor growth and alleviated metabolic rearrangement in both serum and tumor of A549 xenograft mice. Among these endogenous metabolites, 3-hydroxybutyric acid (3-HB) was significantly increased in serum, tumor and liver after apatinib treatment. Interestingly, giving exogenous 3-HB also inhibited tumor growth. Gene expression, dual luciferase reporter gene assay and molecular docking analysis all indicated that apatinib could induce 3-HB production through the dependent activation of peroxisome proliferator-activated receptor α (PPARα) and promotion of fatty acid utilization in the liver. Therefore, increased content of 3-HB induced by PPARα activation in the liver partially contributed to the antitumor effect of apatinib. It may provide clues to another potential mechanism underlying the antitumor effect of apatinib besides its antiangiogenic effect through inhibiting vascular endothelial growth factor receptor 2.
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Registered trials
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.