title: Rosiglitazone suppresses angiogenesis in multiple myeloma via downregulation of hypoxia-inducible factor-1α and insulin-like growth factor-1 mRNA expression.
abstract: Rosiglitazone (RGZ) is a thiazolidinedione ligand of peroxisome proliferator-activated receptor-γ. Our previous studies have confirmed that RGZ possesses antitumoral properties. Bone marrow angiogenesis exhibits an important role in multiple myeloma (MM), and angiogenesis often correlates with the prognosis and disease burden of MM. However, to the best of our knowledge, inhibition of angiopoiesis by RGZ in MM has not yet been reported. The present study aimed to investigate whether RGZ prevents angiogenesis and the possible underlying mechanism of this effect in MM. RPMI‑8226 cells, primary myeloma cells from patients with MM or mononuclear cells from healthy patients were treated with different concentrations of RGZ, and various biological responses were detected using MTT, reverse transcription-polymerase chain reaction and western blot assays. The expression levels of hypoxia-inducible transcription factor‑1α (HIF1α) and insulin-like growth factor‑1 (IGF1) were significantly increased in the RPMI-8226 cells and the primary myeloma cells from the patients with MM compared with those in the mononuclear cells from the healthy patients. The results also showed that RGZ was able to inhibit proliferation and reduce viability of RPMI-8226 cells in a concentration-and time-dependent manner. RGZ was able to concentration‑dependently inhibit the expression of HIF1α and IGF1 mRNA in RPMI-8226 and primary myeloma cells from patients with MM. RGZ also inhibited the expression of pAKT and downregulated the expression levels of phosphorylated extracellular signal-regulated kinase (ERK) in RPMI-8226 cells. The results suggested that RGZ inhibits the angiopoiesis of tumors by interfering with the phosphatidylinositol 3-kinase/AKT and ERK signaling pathways.
authors: Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors: Mingzhong
authors: M
authors: Rui
authors: Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors: Zhanping
authors: Z
authors: Huang
authors: Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors: Ying
authors: Y
authors: Liu
authors: Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors: Ziyan
authors: Z
authors: Wang
authors: Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors: Rui
authors: R
authors: Liu
authors: Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors: Jinxiang
authors: J
authors: Fu
authors: Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors: Haiwen
authors: H
authors: Huang
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D007004:Hypoglycemic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases