[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.4196/kjpp.2020.24.3.241

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)

Publication Information

The Korean Journal of Physiology and Pharmacology / v.24, no.3, 2020 , pp. 241-248 More about this Journal

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

Keywords

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

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