LAUSR

As a nuclear receptor, peroxisome-proliferator-activated receptor α (PPARα) plays a critical role in regulation of metabolism and cancer, while the effect of PPARα agonist on cancer cell glucose metabolism-linked tumor growth is still unclear. Here we found that PPARα agonist (Wy14,643) decreased Glut1 (Glucose transporter 1) gene and protein expressions of colorectal cancer cell lines in response to normoxia or hypoxia. Dual-luciferase analysis showed that Wy14,643 inhibited Glut1 transcription activity. Importantly, ChIP-qPCR analysis showed that Wy14,643 increased the binding of PPARα to Glut1 promoter region. Wy14,643 suppressed Glut1 transcription activity resulting in reduced influx of glucose in cancer cells in response to normoxia or hypoxia. Further analysis showed that Wy14,643-mediated inhibition of tumor growth and chemo-resistance was associated with inhibition of mTOR pathway. Taken together, PPARα agonist Wy14,643 suppressed Glut1 transcription activity, glucose uptake and mTOR pathway in colorectal cancer cells, which was involved in reduced tumor growth and chemo-resistance. These findings provided a novel therapy strategy for cancer progression.