Metformin inhibits PPARδ agonist-mediated tumor growth by reducing Glut1 and SLC1A5 expressions of cancer cells.
As a nuclear receptor, ligand binding and activated PPARδ (peroxisome-proliferator-activated receptor δ) plays an important role in regulation of inflammation, metabolism and cancer, while it is unclear the effect of metformin on PPARδ-mediated cancer cell metabolism. Here we found that PPARδ agonist GW501516 significantly increased Glut1 (Glucose transporter 1) and SLC1A5 (solutecarrier family 1 member 5) gene and protein expressions in HCT-116, SW480, HeLa, and MCF-7 cancer cell lines, while metformin inhibited this event, which was associated with metformin-mediated inhibition of PPARδ activity in response to GW501516. Importantly, GW501516 inhibited the binding of PPARδ to AMPK, while metformin reversed this process. Metformin inhibited Glut1 and SLC1A5 expressions leading to reduced influx of glucose and glutamine in cancer cells, which is associated with reduced tumor growth. These findings suggest that metformin inhibited PPARδ agonist GW501516-induced cancer cell metabolism and tumor growth.
['Ding|Jiajun|J|', 'Gou|Qian|Q|', 'Jin|Jianhua|J|', 'Shi|Juanjuan|J|', 'Liu|Qian|Q|', 'Hou|Yongzhong|Y|']
D026962:Amino Acid Transport System ASC D000818:Animals D000970:Antineoplastic Agents D045744:Cell Line, Tumor D049109:Cell Proliferation D005260:Female D015972:Gene Expression Regulation, Neoplastic D005947:Glucose D051272:Glucose Transporter Type 1 D005973:Glutamine D006801:Humans D008687:Metformin D051379:Mice D015778:Minor Histocompatibility Antigens D047494:PPAR delta D013844:Thiazoles D014158:Transcription, Genetic D023041:Xenograft Model Antitumor Assays
Metformin PPARδ Glut1 SLC1A5 GW501516 AMPK Transcriptional activity