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Type: Artigo de periódico
Title: Antineoplastic effect of rapamycin is potentiated by inhibition of IRS-1 signaling in prostate cancer cells xenografts
Author: Oliveira, JC
Souza, KK
Dias, MM
Faria, MC
Ropelle, ER
Flores, MBS
Ueno, M
Velloso, LA
Saad, ST
Saad, MJA
Carvalheira, JBC
Abstract: Proper activation of phosphoinositide 3-kinase-Akt pathway is critical for the prevention of tumorigenesis. Recent data have characterized a negative feedback loop, wherein mammalian target of rapamycin (mTOR) blocks additional activation of the Akt/mTOR pathway through inhibition insulin receptor substrate 1 (IRS-1) function. However, the potential of IRS-1 inhibition during rapamycin treatment has not been examined. Herein, we show that IRS-1 antisense oligonucleotide and rapamycin synergistically antagonize the activation of mTOR in vivo and induced tumor suppression, through inhibition of proliferation and induction of apoptosis, in prostate cancer cell xenografts. These data demonstrate that the addition of agents that blocks IRS-1 potentiate the effect of mTOR inhibition in the growth of prostate cancer cell xenografts.
Subject: protein kinases
phosphatidylinositol 3-kinase
insulin receptor substrate 1
prostate neoplasms
Country: EUA
Editor: Springer
Rights: fechado
Identifier DOI: 10.1007/s00432-008-0359-5
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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