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The Influence Of Rosiglitazone On The Expression Of HIF1α And IGF1in Myeloma Cells And The Study Of Its Possible Mechanism

Posted on:2015-04-11Degree:MasterType:Thesis
Country:ChinaCandidate:M Z RuiFull Text:PDF
GTID:2284330428499616Subject:Internal Medicine
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Part I:The influence of rosiglitazone on the proliferation and expression ofHIF1α and IGF1of myeloma cells and primary myeloma cellsObjective:To observe the effect of rosiglitazone(RGZ) on myeloma cell proliferationand expression of HIF1α and IGF1mRNA.Methods:The expression of HIF1α and IGF1mRNA was detected in five newlydiagnosed MM patients and five iron deficiency anemia (control group) by RT-PCR.RPMI8226and primary myeloma cells from patients were treated with differentconcentrations of RGZ, MTT was used to detect the proliferation, the expression of HIF1αand IGF1mRNAwas analyzed after48h by RT-PCR.Results:We demonstrate a high expression of HIF1α and IGF1in RPMI8226and inprimary myeloma cells, the exposure to RGZ induced proliferation inhibition inRPMI8226in a dose-dependent manner and a significant decrease was observed in themRNAexpression of HIF1α and IGF1in RPMI8226and in primary myeloma cells.Conclusion:Our results suggest that rosiglitazone could inhibit RPMI8226cellsgrowth and the expression of HIF1α and IGF1mRNA. Part II:The influence of rosiglitazone on the expression of AKT and ERK inmyeloma cellsObjective:To observe the effect of rosiglitazone(RGZ) on the expression of AKTand ERK in the myeloma cells and to explore the possible mechanism. Methods: RPMI8226were treated with different concentrations of RGZ, theexpression of phosphorylated AKT,ERK and total proteins were detected by Westernblotting.Results:RGZ can inhibit pAKT and pERK in RPMI8226cells in a dose-dependentmanner with10,20and40μmol/L. However,the expression of total AKT and ERK proteinshowed no obvious difference.Conclusion:Our results suggest that rosiglitazone may inhibit the expression ofHIF1α and IGF1possibly by interfering with the PI3K/AKT and ERK signaling pathways.
Keywords/Search Tags:Rosiglitazone, Myeloma, HIF1α, IGF1Rosiglitazone, AKT, ERK
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