Objective: To observe the effect of rosiglitazone (RGZ) on the mRNA expression of HIF1α and IGF1 genes in the myeloma cells and explore possible mechanism of angiogenesis inhibition.
Methods: Human myeloma cell line RPMI8226 and primary myeloma cells from five patients enriched by using CD138 immunomagnetic beads were treated with different concentrations (10, 20, 40 μmol/L) of RGZ. The mRNA expression of HIF1α and IGF1 was analyzed in cells treated with RGZ after 48h by RT-PCR, The levels of phosphorylated AKT and ERK proteins were detected by Western blotting. Bone marrow mononuclear cells from five patients with iron deficiency anemia were regarded as control.
Results: Higher mRNA expression of HIF1α and IGF1 genes in RPMI8226 and in primary myeloma cells was showed as compared to those in control. Treated with RGZ of 20 μmol/L after 48 h, the mRNA expression of HIF1α (1.21 ± 0.08 vs 0.75 ± 0.06) and IGF1 (0.62 ± 0.06 vs 0.32 ± 0.04) in RPMI8226 cells was declined as compared to those without RGC treatment. The same declination was also seen in primary myeloma cells (HIF1α: 2.02 ± 0.16 vs 0.53 ± 0.04; IGF1: 1.92 ± 0.13 vs 0.58±0.03). RGZ could inhibit the expression of pAKT and pERK, nor the total AKT and ERK proteins, in RPMI8226 cells in a dose-dependent manner at the concentration of 10 μmol/L, 20 μmol/L, and 40 μmol/L.
Conclusion: RGZ could inhibit the mRNA expression of HIF1α and IGF1. Inhibition of angiogenesis by RGZ may be associated with down-regulation of pAKT and pERK expression.