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Title: Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell

Abstract

Current therapies available for the treatment of human osteosarcoma, an aggressive bone tumor, are insufficient. To examine an alternative approach of integrin-based anti-osteosacoma strategy, acurhagin-C, a Glu-Cys-Asp (ECD)-disintegrin, was isolated and evaluated for its application in combination with two potent inhibitors of basic fibroblast growth factor (bFGF) and interleukin-8 (IL-8). The investigation of human osteosarcoma MG-63 cells pre-incubated with a FGF receptor-1 (FGFR-1) blocker AZD4547, a CXC-chemokine receptor-1/-2 (CXCR1/2) antagonist reparixin, and acurhagin-C via two given modes of separation and combination was executed. Detected by flow cytometry, integrins-α2/-α5/-αv/-β1, FGFR-1, CXCR1 and CXCR2 constitutively express on the resting membrane. However, bFGF/IL-8-activated MG-63 cells only statistically enhanced the surface exposure of integrins-α5/-β1, FGFR-1 and CXCR2. In activated MG-63 cells, acurhagin-C targeting integrin-α5 not only might potentiate the inhibitory effect of AZD4547 and reparixin on the surface expression of integrin-α5, FGFR-1 and CXCR2, but also acurhagin-C used alone remained effectively to diminish the surface exposure of those targeted receptors. Hence, a complicated crosstalk mechanism should be involved in the membrane interactions. Furthermore, co-administration of acurhagin-C with AZD4547 and reparixin also showed to have the synergistic suppression toward cell proliferation and the gene expression of matrix metalloproteinase-2. Also, the administration of three-in-one mode could nearlymore » abrogate the cellular attachment onto collagen-IV- and fibronectin-coated wells, as well as penetration into Matrigel-barrier. These data supported an ECD-disintegrin acurhagin-C targeting integrin-α5 upon combined used with AZD4547 and reparixin may become a promising therapeutic approach for attenuating osteosarcoma development. - Highlights: • Acurhagin-C against integrins exerts the application in anti-osteosacoma therapy. • Acurhagin-C in combination with AZD4547 and reparixin has synergistic inhibitions. • The 3 in 1 treatment can diminish MG-63 cells proliferation and MMP-2 expression. • The 3 in 1 treatment can effectively disturb MG-63 cells adhesion and invasion.« less

Authors:
;  [1];  [1];  [2]
  1. Chang Gung University of Science and Technology, Guishan Dist., Taoyuan City, Taiwan (China)
  2. (China)
Publication Date:
OSTI Identifier:
22719114
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 492; Journal Issue: 3; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; COLLAGEN; FIBROBLASTS; FLUORESCEIN; FLUORESCENCE; INHIBITION; ISOTHIOCYANATES; LYMPHOKINES; MONOCLONAL ANTIBODIES; OSTEOSARCOMAS; POLYMERASE CHAIN REACTION; POLYMERASES; RECEPTORS; SKELETON; THERAPY

Citation Formats

Shih, Chun-Ho, Chiang, Tin-Bin, Wang, Wen-Jeng, and Department of Neurological Surgery, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City, Taiwan. Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.08.046.
Shih, Chun-Ho, Chiang, Tin-Bin, Wang, Wen-Jeng, & Department of Neurological Surgery, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City, Taiwan. Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell. United States. doi:10.1016/J.BBRC.2017.08.046.
Shih, Chun-Ho, Chiang, Tin-Bin, Wang, Wen-Jeng, and Department of Neurological Surgery, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City, Taiwan. Sat . "Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell". United States. doi:10.1016/J.BBRC.2017.08.046.
@article{osti_22719114,
title = {Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell},
author = {Shih, Chun-Ho and Chiang, Tin-Bin and Wang, Wen-Jeng and Department of Neurological Surgery, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan City, Taiwan},
abstractNote = {Current therapies available for the treatment of human osteosarcoma, an aggressive bone tumor, are insufficient. To examine an alternative approach of integrin-based anti-osteosacoma strategy, acurhagin-C, a Glu-Cys-Asp (ECD)-disintegrin, was isolated and evaluated for its application in combination with two potent inhibitors of basic fibroblast growth factor (bFGF) and interleukin-8 (IL-8). The investigation of human osteosarcoma MG-63 cells pre-incubated with a FGF receptor-1 (FGFR-1) blocker AZD4547, a CXC-chemokine receptor-1/-2 (CXCR1/2) antagonist reparixin, and acurhagin-C via two given modes of separation and combination was executed. Detected by flow cytometry, integrins-α2/-α5/-αv/-β1, FGFR-1, CXCR1 and CXCR2 constitutively express on the resting membrane. However, bFGF/IL-8-activated MG-63 cells only statistically enhanced the surface exposure of integrins-α5/-β1, FGFR-1 and CXCR2. In activated MG-63 cells, acurhagin-C targeting integrin-α5 not only might potentiate the inhibitory effect of AZD4547 and reparixin on the surface expression of integrin-α5, FGFR-1 and CXCR2, but also acurhagin-C used alone remained effectively to diminish the surface exposure of those targeted receptors. Hence, a complicated crosstalk mechanism should be involved in the membrane interactions. Furthermore, co-administration of acurhagin-C with AZD4547 and reparixin also showed to have the synergistic suppression toward cell proliferation and the gene expression of matrix metalloproteinase-2. Also, the administration of three-in-one mode could nearly abrogate the cellular attachment onto collagen-IV- and fibronectin-coated wells, as well as penetration into Matrigel-barrier. These data supported an ECD-disintegrin acurhagin-C targeting integrin-α5 upon combined used with AZD4547 and reparixin may become a promising therapeutic approach for attenuating osteosarcoma development. - Highlights: • Acurhagin-C against integrins exerts the application in anti-osteosacoma therapy. • Acurhagin-C in combination with AZD4547 and reparixin has synergistic inhibitions. • The 3 in 1 treatment can diminish MG-63 cells proliferation and MMP-2 expression. • The 3 in 1 treatment can effectively disturb MG-63 cells adhesion and invasion.},
doi = {10.1016/J.BBRC.2017.08.046},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 492,
place = {United States},
year = {2017},
month = {10}
}