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The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro

BACKGROUND: Despite of the recent success of EGFR inhibitory agents, the primary drug-resistant becomes a major challenge for EGFR inhibitor therapies. PTEN gene is an important positive regulatory factor for response to EGFR inhibitor therapy. Low-expression of PTEN is clearly one of the important...

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Autores principales: Zhuang, Hong-Qing, Wang, Jun, Yuan, Zhi-Yong, Zhao, Lu-Jun, Wang, Ping, Wang, Chang-Li
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741431/
https://www.ncbi.nlm.nih.gov/pubmed/19723324
http://dx.doi.org/10.1186/1756-9966-28-123
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author Zhuang, Hong-Qing
Wang, Jun
Yuan, Zhi-Yong
Zhao, Lu-Jun
Wang, Ping
Wang, Chang-Li
author_facet Zhuang, Hong-Qing
Wang, Jun
Yuan, Zhi-Yong
Zhao, Lu-Jun
Wang, Ping
Wang, Chang-Li
author_sort Zhuang, Hong-Qing
collection PubMed
description BACKGROUND: Despite of the recent success of EGFR inhibitory agents, the primary drug-resistant becomes a major challenge for EGFR inhibitor therapies. PTEN gene is an important positive regulatory factor for response to EGFR inhibitor therapy. Low-expression of PTEN is clearly one of the important reasons why tumor cells resisted to tyrosine kinase inhibitors. METHODS: To investigate the drug-resistance reversal to gefitinb and the mechanism in PTEN low expression cells which radiated with X-rays in vitro, We demonstrated that H-157 lung cancer cells (low-expression of PTEN but phospho-EGFR overexpressed tumor cells) exposed to X-rays. The PTEN expressions and radiosensitizing effects of tyrosine kinase inhibitor before and after irradiation were observed. The cell-survival rates were evaluated by colony-forming assays. The cell apoptosis was investigated using FCM. The expressions of phospho-EGFR and PTEN were determined by Western blot analysis. RESULTS: The results showed that the PTEN expressions were significantly enhanced by X-rays. Moreover, the cell growth curve and survival curve were down-regulated in the gefitinib-treated groups after irradiation. Meanwhile, the radiation-induced apoptosis of tumor cells was increased by inhibition of the EGFR through up-regulation of PTEN. CONCLUSION: These results suggested that PTEN gene is an important regulator on TKI inhibition, and the resistance to tyrosine kinase inhibitors might be reversed by irradiation in PTEN low expression cancer cells.
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spelling pubmed-27414312009-09-11 The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro Zhuang, Hong-Qing Wang, Jun Yuan, Zhi-Yong Zhao, Lu-Jun Wang, Ping Wang, Chang-Li J Exp Clin Cancer Res Research BACKGROUND: Despite of the recent success of EGFR inhibitory agents, the primary drug-resistant becomes a major challenge for EGFR inhibitor therapies. PTEN gene is an important positive regulatory factor for response to EGFR inhibitor therapy. Low-expression of PTEN is clearly one of the important reasons why tumor cells resisted to tyrosine kinase inhibitors. METHODS: To investigate the drug-resistance reversal to gefitinb and the mechanism in PTEN low expression cells which radiated with X-rays in vitro, We demonstrated that H-157 lung cancer cells (low-expression of PTEN but phospho-EGFR overexpressed tumor cells) exposed to X-rays. The PTEN expressions and radiosensitizing effects of tyrosine kinase inhibitor before and after irradiation were observed. The cell-survival rates were evaluated by colony-forming assays. The cell apoptosis was investigated using FCM. The expressions of phospho-EGFR and PTEN were determined by Western blot analysis. RESULTS: The results showed that the PTEN expressions were significantly enhanced by X-rays. Moreover, the cell growth curve and survival curve were down-regulated in the gefitinib-treated groups after irradiation. Meanwhile, the radiation-induced apoptosis of tumor cells was increased by inhibition of the EGFR through up-regulation of PTEN. CONCLUSION: These results suggested that PTEN gene is an important regulator on TKI inhibition, and the resistance to tyrosine kinase inhibitors might be reversed by irradiation in PTEN low expression cancer cells. BioMed Central 2009-09-01 /pmc/articles/PMC2741431/ /pubmed/19723324 http://dx.doi.org/10.1186/1756-9966-28-123 Text en Copyright © 2009 Zhuang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Zhuang, Hong-Qing
Wang, Jun
Yuan, Zhi-Yong
Zhao, Lu-Jun
Wang, Ping
Wang, Chang-Li
The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro
title The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro
title_full The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro
title_fullStr The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro
title_full_unstemmed The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro
title_short The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro
title_sort drug-resistance to gefitinib in pten low expression cancer cells is reversed by irradiation in vitro
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741431/
https://www.ncbi.nlm.nih.gov/pubmed/19723324
http://dx.doi.org/10.1186/1756-9966-28-123
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