Heat shock protein 90 inhibitor AUY922 attenuates platelet-derived growth factor-BB-induced migration and proliferation of vascular smooth muscle cells

Jisu Kim, Kang Pa Lee, Bom Sahn Kim, Sang Ju Lee, Byung Seok Moon, Suji Baek

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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-BBinduced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.

Original languageEnglish
Pages (from-to)241-248
Number of pages8
JournalKorean Journal of Physiology and Pharmacology
Volume24
Issue number3
DOIs
StatePublished - 1 May 2020

Keywords

  • AUY922
  • Atherosclerosis
  • Heat shock protein 90
  • Platelet-derived growth factor
  • Vascular disease

Fingerprint

Dive into the research topics of 'Heat shock protein 90 inhibitor AUY922 attenuates platelet-derived growth factor-BB-induced migration and proliferation of vascular smooth muscle cells'. Together they form a unique fingerprint.

Cite this