Résumé
【Objective】 To investigate the effects and molecular mechanism of Elafibranor (ELA) on the proliferation, migration and apoptosis of human prostate cancer (PCa) cells. 【Methods】 After PCa DU145 cells were treated with culture media containing different dosages of ELA, the proliferation, migration and apoptosis were determined with MTT assay, wound healing assay and Transwell assay, respectively. The expressions of genes related to lipid metabolism were detected with real-time quantitative polymerase chain reaction (real-time qPCR). 【Results】 The relative cell proliferation rate at 48 h was 100% in the blank control group, (86.9±7.8)% in the low-dose (5 μmol/L) group and (58.5±9.4)% in the high-dose (15 μmol/L) group;the wound healing rate at 24 h was (74.7±3.2)%, (61.8±2.9)% and (53.2±3.3)%;the relative percentage of migrated cells at 24 h was 100%, (32.4±11.2)% and (15.4±3.2)%;the cell apoptosis rate at 48 h was (9.3±1.4)%, (11.3±0.3)%, and (15.2±4.5)%, respectively, all P<0.05. After ELA treatment for 48 h, the genes related to fatty acid intake (SCPX, PLTP) and fatty acid oxidation (PDK1, ACOX2) were significantly down-regulated in the high-dose group, while the gene related to fatty acid deposition (PLIN2) was significantly up-regulated, indicating that the lipid metabolism pathway of DU145 cells was seriously interfered by the ELA treatment. 【Conclusion】 ELA can inhibit the proliferation and migration, and promote the apoptosis of prostate cancer cells by interfering in the lipid metabolism pathway, which exhibits remarkable potential of clinical translation in the field of anti-tumor chemotherapy.
Résumé
Non-alcoholic fatty liver disease (NAFLD) represents an increasing health problem in Chile and worldwide. In some cases NAFLD presents with a progressive form that can lead to liver fibrosis, cirrhosis and hepatocellular carcinoma. Current pharmacological therapies (pioglitazone and vitamin E) show limited response and are associated to significant adverse effects. During recent years several novel and promising pharmacological therapies have been developed to prevent fibrosis, liver cirrhosis and reduce liver related deaths. The present article summarizes some of these promising strategies, including reported efficacy in clinical trials and associated adverse effects. Hopefully in the near future these new therapies will help to improve NAFLD management and reduce liver related complications.
El hígado graso no alcohólico (HGNA) es un creciente problema de salud pública en Chile y el mundo. En un subgrupo de sujetos, el HGNA puede presentarse con un fenotipo de daño hepático progresivo que puede evolucionar a fibrosis progresiva, cirrosis y carcinoma hepatocelular. Las estrategias farmacológicas actuales (pioglitazona y vitamina E) presentan eficacia limitada y no están exentas de efectos adversos. Durante los últimos años se han desarrollado múltiples estrategias farmacológicas novedosas y promisorias que buscan evitar la progresión hacia cirrosis y reducir la mortalidad de causa hepática. El presente artículo resume los principales nuevos fármacos, los efectos beneficiosos reportados y sus efectos adversos. Es de esperar que en un futuro próximo estas terapias permitan cambiar el pronóstico de nuestros pacientes con HGNA.