Inhibition of STAT3 and ErbB2 Suppresses Tumor Growth, Enhances Radiosensitivity, and Induces Mitochondria-Dependent Apoptosis in Glioma Cells

Ling, Gao; Fengsheng, Li; Bo, Dong; Junquan, Zhang; Yalan, Rao; Yue, Cong; Bingzhi, Mao

Title: Inhibition of STAT3 and ErbB2 Suppresses Tumor Growth, Enhances Radiosensitivity, and Induces Mitochondria-Dependent Apoptosis in Glioma Cells

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Abstract

Purpose: Constitutively activated signal transducer and activator of transcription 3 (STAT3) and ErbB2 are involved in the pathogenesis of many tumors, including astrocytoma. Inactivation of these molecules is reported to result in radiosensitization. The purpose of this study was to investigate whether inhibition of STAT3, ErbB2, or both could enhance radiotherapy in the human glioma model (U251 and U87 cell lines). Methods and Materials: The RNAi plasmids targeting STAT3 or ErbB2 were constructed, and their downregulatory effects on target proteins were examined by immunoblotting. After combination treatment of RNAi with or without irradiation, the cell viability was determined using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and clonogenic assays. The in vivo effect of combined treatment was determined using the U251 xenograft model. The apoptosis caused by the inhibition of STAT3 and ErbB2 was detected, and the mechanism involved in the apoptosis was investigated, including increases in caspase proteins, mitochondrial damage, and the expression of key modulating protein of different apoptosis pathways. Results: Transfection of U251 cells with STAT3 or ErbB2 siRNA plasmids specifically reduced their target gene expressions. Inhibition of STAT3 or ErbB2 greatly decreased glioma cell survival after 2, 4, or 6 Gy irradiation. Inhibition of STAT3 and ErbB2 also enhanced radiation-inducedmore »« less

Authors:

Ling, Gao; Fengsheng, Li; Bo, Dong; Junquan, Zhang; Yalan, Rao; Yue, Cong; Bingzhi, Mao ^[1]

Department of Experimental Therapy of ARS, Beijing Institute of Radiation Medicine, Beijing (China)

Publication Date:: Thu Jul 15 00:00:00 EDT 2010

OSTI Identifier:: 21451140

Resource Type:: Journal Article

Journal Name:: International Journal of Radiation Oncology, Biology and Physics

Additional Journal Information:: Journal Volume: 77; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2009.12.036; PII: S0360-3016(09)03702-X; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0360-3016

Country of Publication:: United States

Language:: English

Subject:: 63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; APOPTOSIS; GLIOMAS; GROWTH; INHIBITION; MITOCHONDRIA; PLASMIDS; PROTEINS; RADIOSENSITIVITY; RADIOTHERAPY; TETRAZOLIUM; AZOLES; CELL CONSTITUENTS; CHLORIDES; CHLORINE COMPOUNDS; DISEASES; HALIDES; HALOGEN COMPOUNDS; HETEROCYCLIC COMPOUNDS; MEDICINE; NEOPLASMS; NERVOUS SYSTEM DISEASES; NUCLEAR MEDICINE; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; RADIOLOGY; SENSITIVITY; TETRAZOLES; THERAPY

Citation Formats


                    Ling, Gao, Fengsheng, Li, Bo, Dong, Junquan, Zhang, Yalan, Rao, Yue, Cong, Bingzhi, Mao, and Chen Xiaohua, E-mail: chenxh@nic.bmi.ac.c. Inhibition of STAT3 and ErbB2 Suppresses Tumor Growth, Enhances Radiosensitivity, and Induces Mitochondria-Dependent Apoptosis in Glioma Cells.  United States: N. p., 2010. 
        Web.

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                    Ling, Gao, Fengsheng, Li, Bo, Dong, Junquan, Zhang, Yalan, Rao, Yue, Cong, Bingzhi, Mao, & Chen Xiaohua, E-mail: chenxh@nic.bmi.ac.c. Inhibition of STAT3 and ErbB2 Suppresses Tumor Growth, Enhances Radiosensitivity, and Induces Mitochondria-Dependent Apoptosis in Glioma Cells.  United States.

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                    Ling, Gao, Fengsheng, Li, Bo, Dong, Junquan, Zhang, Yalan, Rao, Yue, Cong, Bingzhi, Mao, and Chen Xiaohua, E-mail: chenxh@nic.bmi.ac.c. 2010.  
        "Inhibition of STAT3 and ErbB2 Suppresses Tumor Growth, Enhances Radiosensitivity, and Induces Mitochondria-Dependent Apoptosis in Glioma Cells".  United States.

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@article{osti_21451140,

  title        = {Inhibition of STAT3 and ErbB2 Suppresses Tumor Growth, Enhances Radiosensitivity, and Induces Mitochondria-Dependent Apoptosis in Glioma Cells},

  author       = {Ling, Gao and Fengsheng, Li and Bo, Dong and Junquan, Zhang and Yalan, Rao and Yue, Cong and Bingzhi, Mao and Chen Xiaohua, E-mail: chenxh@nic.bmi.ac.c},

  abstractNote = {Purpose: Constitutively activated signal transducer and activator of transcription 3 (STAT3) and ErbB2 are involved in the pathogenesis of many tumors, including astrocytoma. Inactivation of these molecules is reported to result in radiosensitization. The purpose of this study was to investigate whether inhibition of STAT3, ErbB2, or both could enhance radiotherapy in the human glioma model (U251 and U87 cell lines). Methods and Materials: The RNAi plasmids targeting STAT3 or ErbB2 were constructed, and their downregulatory effects on target proteins were examined by immunoblotting. After combination treatment of RNAi with or without irradiation, the cell viability was determined using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and clonogenic assays. The in vivo effect of combined treatment was determined using the U251 xenograft model. The apoptosis caused by the inhibition of STAT3 and ErbB2 was detected, and the mechanism involved in the apoptosis was investigated, including increases in caspase proteins, mitochondrial damage, and the expression of key modulating protein of different apoptosis pathways. Results: Transfection of U251 cells with STAT3 or ErbB2 siRNA plasmids specifically reduced their target gene expressions. Inhibition of STAT3 or ErbB2 greatly decreased glioma cell survival after 2, 4, or 6 Gy irradiation. Inhibition of STAT3 and ErbB2 also enhanced radiation-induced tumor growth inhibition in the U251 xenograft model. Furthermore, the suppression of either STAT3 or ErbB2 could induce U251 cell apoptosis, which was related primarily to the mitochondrial apoptotic pathway. Conclusions: These results indicated that simultaneous inhibition of STAT3 and ErbB2 expression can promote potent antitumor activity and radiosensitizing activity in human glioma.},

  doi          = {},

  url          = {https://www.osti.gov/biblio/21451140},
  journal      = {International Journal of Radiation Oncology, Biology and Physics},

  issn         = {0360-3016},

  number       = 4,

  volume       = 77,

  place        = {United States},

  year         = {Thu Jul 15 00:00:00 EDT 2010},

  month        = {Thu Jul 15 00:00:00 EDT 2010}

}

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