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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 2013-04, Vol.29 (4), p.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:
AKT
Src
Publisher: Greece: D.A. Spandidos
ID: ISSN: 1021-335X
Link: https://www.ncbi.nlm.nih.gov/pubmed/23338526
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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:
  • AKT
  • Animals
  • Apoptosis
  • Apoptosis - drug effects
  • Brain Neoplasms - drug therapy
  • Brain Neoplasms - genetics
  • Brain Neoplasms - pathology
  • Cell division
  • Cell growth
  • Cell Line, Tumor
  • Chemotherapy
  • Cytotoxicity
  • Dacarbazine - administration & dosage
  • Dacarbazine - analogs & derivatives
  • Down-Regulation
  • Gene expression
  • Gene Expression Regulation, Neoplastic - drug effects
  • Glioblastoma - drug therapy
  • Glioblastoma - genetics
  • Glioblastoma - pathology
  • glioma
  • Glioma - drug therapy
  • Glioma - genetics
  • Glioma - pathology
  • Growth factors
  • Humans
  • Kinases
  • Mice
  • Oncogene Protein v-akt - antagonists & inhibitors
  • Oncogene Protein v-akt - genetics
  • Protein expression
  • Proteins
  • Signal Transduction - drug effects
  • Src
  • src-Family Kinases - genetics
  • Studies
  • temozolomide
  • Variance analysis
  • Xenograft Model Antitumor Assays
ispartof: Oncology reports, 2013-04, Vol.29 (4), p.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
fulltext: no_fulltext
issn:
  • 1021-335X
  • 1791-2431
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
creatorcontribWANG, ZENGGUANG ; SUN, JIKUI ; LI, XUE ; YANG, SHUYUAN ; YUE, SHUYUAN ; ZHANG, JIANNING ; YANG, XUEJUN ; ZHU, TAO ; JIANG, RONGCAI ; YANG, WEIDONG
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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subjectAKT ; Animals ; Apoptosis ; Apoptosis - drug effects ; Brain Neoplasms - drug therapy ; Brain Neoplasms - genetics ; Brain Neoplasms - pathology ; Cell division ; Cell growth ; Cell Line, Tumor ; Chemotherapy ; Cytotoxicity ; Dacarbazine - administration & dosage ; Dacarbazine - analogs & derivatives ; Down-Regulation ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Glioblastoma - drug therapy ; Glioblastoma - genetics ; Glioblastoma - pathology ; glioma ; Glioma - drug therapy ; Glioma - genetics ; Glioma - pathology ; Growth factors ; Humans ; Kinases ; Mice ; Oncogene Protein v-akt - antagonists & inhibitors ; Oncogene Protein v-akt - genetics ; Protein expression ; Proteins ; Signal Transduction - drug effects ; Src ; src-Family Kinases - genetics ; Studies ; temozolomide ; Variance analysis ; Xenograft Model Antitumor Assays
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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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5Brain Neoplasms - genetics
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7Cell division
8Cell growth
9Cell Line, Tumor
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15Gene expression
16Gene Expression Regulation, Neoplastic - drug effects
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30Protein expression
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titleDownregulation of Src enhances the cytotoxic effect of temozolomide through AKT in glioma
authorWANG, ZENGGUANG ; SUN, JIKUI ; LI, XUE ; YANG, SHUYUAN ; YUE, SHUYUAN ; ZHANG, JIANNING ; YANG, XUEJUN ; ZHU, TAO ; JIANG, RONGCAI ; YANG, WEIDONG
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8Cell growth
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pages1395-1398
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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.
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