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Downregulation of Src enhances the cytotoxic effect of temozolomide through AKT in glioma

Src is an attractive target since it is overexpressed in a number of malignancies, including glioma. However, the mechanism of Src signaling as well as its silencing effect on temozolomide in glioma is not well known. We hypothesized that downregulation of Src may enhance the cytotoxic effect of tem... Full description

Journal Title: Oncology Reports 4/2013, Vol.29(4), pp.1395-1398
Main Author: Wang, Zengguang
Other Authors: Sun, Jikui , Li, Xue , Yang, Shuyuan , Yue, Shuyuan , Zhang, Jianning , Yang, Xuejun , Zhu, Tao , Jiang, Rongcai , Yang, Weidong
Format: Electronic Article Electronic Article
Language: English
Subjects:
Src
Akt
ID: ISSN: 1021-335X ; E-ISSN: 1791-2431 ; DOI: 10.3892/or.2013.2240
Link: http://www.spandidos-publications.com/or/29/4/1395
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recordid: spandido10.3892/or.2013.2240
title: Downregulation of Src enhances the cytotoxic effect of temozolomide through AKT in glioma
format: Article
creator:
  • Wang, Zengguang
  • Sun, Jikui
  • Li, Xue
  • Yang, Shuyuan
  • Yue, Shuyuan
  • Zhang, Jianning
  • Yang, Xuejun
  • Zhu, Tao
  • Jiang, Rongcai
  • Yang, Weidong
subjects:
  • Glioma
  • Src
  • Temozolomide
  • Akt
ispartof: Oncology Reports, 4/2013, Vol.29(4), pp.1395-1398
description: Src is an attractive target since it is overexpressed in a number of malignancies, including glioma. However, the mechanism of Src signaling as well as its silencing effect on temozolomide in glioma is not well known. We hypothesized that downregulation of Src may enhance the cytotoxic effect of temozolomide on glioma. As expected, Src was overexpressed in glioblastoma multiforme (GBM) compared with normal brain tissues. Src silencing suppressed tumor proliferation and induced apoptosis in glioma. In addition, Src silencing combined with temozolomide treatment resulted in significant inhibition of tumor growth. These effects may be mediated by AKT which is a downstream effector of Src, since downregulation of AKT exhibited a similar effect as Src siRNA when combined with temozolomide. Finally, we demonstrated that overexpression of AKT suppressed the enhanced cytotoxic effect of temozolomide mediated by Src silencing. Thus, the present study demonstrated that Src plays a biologically significant role in tumor proliferation and apoptosis and enhances the cytotoxic effect of temozolomide through AKT supression in glioma.
language: eng
source:
identifier: ISSN: 1021-335X ; E-ISSN: 1791-2431 ; DOI: 10.3892/or.2013.2240
fulltext: fulltext
issn:
  • 1021-335X
  • 1021335X
  • 1791-2431
  • 17912431
url: Link


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titleDownregulation of Src enhances the cytotoxic effect of temozolomide through AKT in glioma
creatorWang, Zengguang ; Sun, Jikui ; Li, Xue ; Yang, Shuyuan ; Yue, Shuyuan ; Zhang, Jianning ; Yang, Xuejun ; Zhu, Tao ; Jiang, Rongcai ; Yang, Weidong
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subjectGlioma ; Src ; Temozolomide ; Akt
descriptionSrc is an attractive target since it is overexpressed in a number of malignancies, including glioma. However, the mechanism of Src signaling as well as its silencing effect on temozolomide in glioma is not well known. We hypothesized that downregulation of Src may enhance the cytotoxic effect of temozolomide on glioma. As expected, Src was overexpressed in glioblastoma multiforme (GBM) compared with normal brain tissues. Src silencing suppressed tumor proliferation and induced apoptosis in glioma. In addition, Src silencing combined with temozolomide treatment resulted in significant inhibition of tumor growth. These effects may be mediated by AKT which is a downstream effector of Src, since downregulation of AKT exhibited a similar effect as Src siRNA when combined with temozolomide. Finally, we demonstrated that overexpression of AKT suppressed the enhanced cytotoxic effect of temozolomide mediated by Src silencing. Thus, the present study demonstrated that Src plays a biologically significant role in tumor proliferation and apoptosis and enhances the cytotoxic effect of temozolomide through AKT supression in glioma.
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titleDownregulation of Src enhances the cytotoxic effect of temozolomide through AKT in glioma
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abstractSrc is an attractive target since it is overexpressed in a number of malignancies, including glioma. However, the mechanism of Src signaling as well as its silencing effect on temozolomide in glioma is not well known. We hypothesized that downregulation of Src may enhance the cytotoxic effect of temozolomide on glioma. As expected, Src was overexpressed in glioblastoma multiforme (GBM) compared with normal brain tissues. Src silencing suppressed tumor proliferation and induced apoptosis in glioma. In addition, Src silencing combined with temozolomide treatment resulted in significant inhibition of tumor growth. These effects may be mediated by AKT which is a downstream effector of Src, since downregulation of AKT exhibited a similar effect as Src siRNA when combined with temozolomide. Finally, we demonstrated that overexpression of AKT suppressed the enhanced cytotoxic effect of temozolomide mediated by Src silencing. Thus, the present study demonstrated that Src plays a biologically significant role in tumor proliferation and apoptosis and enhances the cytotoxic effect of temozolomide through AKT supression in glioma.
pubD.A. Spandidos
doi10.3892/or.2013.2240