Effect of rosiglitazone on the expression of HIF1α and IGF1 mRNA in myeloma.
- Author:
Mingzhong RUI
1
;
Tianwen FU
1
;
Ying LIU
1
;
Haiwen HUANG
1
;
Jinxiang FU
1
Author Information
- Publication Type:Journal Article
- MeSH: Cell Line, Tumor; Extracellular Signal-Regulated MAP Kinases; metabolism; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; genetics; metabolism; Insulin-Like Growth Factor I; genetics; metabolism; Multiple Myeloma; blood supply; metabolism; Neovascularization, Pathologic; Proto-Oncogene Proteins c-akt; metabolism; RNA, Messenger; genetics; Thiazolidinediones; pharmacology
- From: Chinese Journal of Hematology 2014;35(7):641-644
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSHuman 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.
RESULTSHigher 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.
CONCLUSIONRGZ 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.
