ArticleBMC cancer2019
PPARα ligand, AVE8134, and cyclooxygenase inhibitor therapy synergistically suppress lung cancer growth and metastasis.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- The Function of PPARα in Cancer Drug Development: A Promising Target for Cancer Treatment.Current cancer drug targets · 2026Review
- The inhibitory effect and targets of CRM197 on tumor growth in arsenic-transformed cells and lung cancer cells.Scientific reports · 2025Article
- Targeting PPARα activation sensitizes glioblastoma cells to temozolomide and reverses acquired resistance by inhibiting H3K18 lactylation.Acta pharmacologica Sinica · 2025Article
- NIR light-propelled Janus Polydopamine@Mesoporous silica gene delivery nanomotor for the enhanced gene treatment of critical limb ischemia.Materials today. Bio · 2025Article
- Article
- Identifying Genetic Signatures Associated with Oncogene-Induced Replication Stress in Osteosarcoma and Screening for Potential Targeted Drugs.Biochemical genetics · 2024Article
- Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease.International journal of molecular sciences · 2023Review
- Metabolic genes, a potential predictor of prognosis and immunogenicity of clear cell renal cell carcinoma.American journal of cancer research · 2023Article
- The Effect ofBioMed research international · 2023Article
- Trends in Subcutaneous Tumour Height and Impact on Measurement Accuracy.Cancer informatics · 2023Article
- WY-14643 attenuates lipid deposition via activation of the PPARα/CPT1A axis by targeting Gly335 to inhibit cell proliferation and migration in ccRCC.Lipids in health and disease · 2022Article
- Review
- Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.Signal transduction and targeted therapy · 2021Review
- PPAR-α Modulators as Current and Potential Cancer Treatments.Frontiers in oncology · 2021Review
- Exploring conformational changes of PPAR-Ɣ complexed with novel kaempferol, quercetin, and resveratrol derivatives to understand binding mode assessment: a small-molecule checkmate to cancer therapy.Journal of molecular modeling · 2020Article
- PPARs and Angiogenesis-Implications in Pathology.International journal of molecular sciences · 2020Review
- Ubiquitin C-Terminal Hydrolase L5 (UCHL5) Accelerates the Growth of Endometrial Cancer via Activating the Wnt/β-Catenin Signaling Pathway.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundLung cancer (LC) is one of the leading causes of death worldwide, which highlights the urgent need for better therapies. Peroxisome proliferator-activated nuclear receptor alpha (PPARα), known as a key nuclear transcription factor involved in glucose and lipid metabolism, has been also implicated in endothelial proliferation and angiogenesis. However, the effects and potential mechanisms of the novel PPARα ligand, AVE8134, on LC growth and progression remain unclear.
methodsA subcutaneous tumour was established in mice by injecting TC-1 lung tumour cells (~ 1 × 10
resultsThe pharmacodynamics effects of AVE8134, Wyeth-14,643, and Bezafibrate on lipids control were similar. However, their effects on tumour suppression were different. Eicosanoid profile analysis showed that all PPARα ligands reduced the production of AA-derived epoxyeicosatrienoic acids (EETs) and increased the hydroxyl product, 11-hydroxyeicosatetraenoic acids (11-HETE). Moreover, increased 11-HETE promoted endothelial proliferation, angiogenesis, and subsequent tumour deterioration in a dose-dependent manner possibly via activating the AKT/extracellular signal-regulated kinase (ERK) pathway. The increased 11-HETE partly neutralized the benefits provided by the Cyp2c44-EETs system inhibited by PPARα ligands in tumour-bearing mice. AVE8134 treatment worsened the tumour phenotype in Cyp2c44 knockout mice, indicating that AVE8134 has contradictory effects on tumour growth. The COX inhibitor indomethacin strengthened the inhibitory actions of AVE8134 on tumour growth and metastasis by inhibiting the 11-HETE production in vivo and in vitro.
conclusionIn this study, we found that the degrees of inhibition on LC growth and metastasis by PPARα ligands depended on their bidirectional regulation on EETs and 11-HETE. Considering their safety and efficacy, the novel PPARα ligand, AVE8134, is a potentially ideal anti-angiogenesis drug for cancer treatment when jointly applied with the COX inhibitor indomethacin.
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