The Korean Journal of Physiology and Pharmacology

  • 제24권3호
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  • Pages.241-248
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  • 2020
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Heat shock protein 90 inhibitor AUY922 attenuates platelet-derived growth factor-BB-induced migration and proliferation of vascular smooth muscle cells

  • Kim, Jisu (Department of Sports Medicine and Science in Graduate School, Konkuk University) ;
  • Lee, Kang Pa (Research & Development Center, UMUST R&D Corporation) ;
  • Kim, Bom Sahn (Department of Nuclear Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine) ;
  • Lee, Sang Ju (Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Moon, Byung Seok (Department of Nuclear Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine) ;
  • Baek, Suji (Research & Development Center, UMUST R&D Corporation)
  • 투고 : 2019.12.05
  • 심사 : 2020.03.25
  • 발행 : 2020.05.01
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초록

Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922-mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BB-induced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.

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