PGC-1a integrates glucose metabolism and angiogenesis in multiple myeloma cells by regulating VEGF and GLUT-4

Human peroxisome proliferator-activated receptor- coactivator 1 (PGC-1) is a key coactivator in the regulation of gene transcriptional activity in normal tissues. However, it is not clear whether it is involved in the angiogenesis and metabolism of multiple myeloma (MM). The aim of the present study was to investigate the role of PGC-1 in MM. Small interfering RNA (siRNA) was used to inhibit PGC-1 expression in RPMI-8226 cells. An endothelial cell migration assay was performed using Transwell chambers and the expression of PGC-1, estrogen-related receptor- (ERR-), vascular endothelial growth factor (VEGF) and glucose transporter-4 (GLUT-4) was tested by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of PGC-1, ERR- and GLUT-4 was assayed by western blot analysis. Lastly, RPMI-8226 cell proliferation was evaluated using CCK-8 assay. VEGF and GLUT-4 mRNA levels were decreased in cells treated with siRNA targeting PGC-1, as was the level of GLUT-4 protein. Endothelial cell migration was significantly reduced when these cells were cultured with culture medium from RPMI-8226 cells treated with siPGC-1. The proliferation rates at 24 and 48 h were suppressed by PGC-1 inhibition. Our results showed that inhibition of PGC-1 suppresses cell proliferation probably by downregulation of VEGF and GLUT-4. The present study suggests that PGC-1 integrates angiogenesis and glucose metabolism in myeloma through regulation of VEGF and GLUT-4.