Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell Carcinoma

It has been demonstrated that mTOR/p70S6K pathway was abnormally activated in many cancers and rapamycin and its analogs can restrain tumor growth through inhibiting this pathway, but some tumors including esophageal squamous cell carcinoma (ESCC) appear to be insensitive to rapamycin in recent stud...

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Main Authors: Zhaoming Lu, Kezheng Peng, Ning Wang, Hong-Min Liu, Guiqin Hou
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2016/7828916
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author Zhaoming Lu
Kezheng Peng
Ning Wang
Hong-Min Liu
Guiqin Hou
author_facet Zhaoming Lu
Kezheng Peng
Ning Wang
Hong-Min Liu
Guiqin Hou
author_sort Zhaoming Lu
collection DOAJ
description It has been demonstrated that mTOR/p70S6K pathway was abnormally activated in many cancers and rapamycin and its analogs can restrain tumor growth through inhibiting this pathway, but some tumors including esophageal squamous cell carcinoma (ESCC) appear to be insensitive to rapamycin in recent studies. In the present study, we explored the measures to improve the sensitivity of ESCC cells to rapamycin and identified the clinical significance of the expression of phosphorylated p70S6K (p-p70S6K). The results showed that, after downregulating the expression of p70S6K and p-p70S6K by p70S6K siRNA, the inhibitory effects of rapamycin on cell proliferation, cell cycle, and tumor growth were significantly enhanced in vitro and in vivo. Furthermore, p-p70S6K had strong positive expression in ESCC tissues and its expression was closely related to lymph node metastasis and the TNM staging. These results indicated that p-p70S6K may participate in the invasion and metastasis in the development of ESCC and downregulation of the expression of p-p70S6K could improve the sensitivity of cells to rapamycin in ESCC.
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spelling doaj-art-bf12f7e226054b1fbde413027c5f520a2025-02-03T01:22:34ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/78289167828916Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell CarcinomaZhaoming Lu0Kezheng Peng1Ning Wang2Hong-Min Liu3Guiqin Hou4School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, ChinaInstitute of Medicine, Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan 450052, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, ChinaIt has been demonstrated that mTOR/p70S6K pathway was abnormally activated in many cancers and rapamycin and its analogs can restrain tumor growth through inhibiting this pathway, but some tumors including esophageal squamous cell carcinoma (ESCC) appear to be insensitive to rapamycin in recent studies. In the present study, we explored the measures to improve the sensitivity of ESCC cells to rapamycin and identified the clinical significance of the expression of phosphorylated p70S6K (p-p70S6K). The results showed that, after downregulating the expression of p70S6K and p-p70S6K by p70S6K siRNA, the inhibitory effects of rapamycin on cell proliferation, cell cycle, and tumor growth were significantly enhanced in vitro and in vivo. Furthermore, p-p70S6K had strong positive expression in ESCC tissues and its expression was closely related to lymph node metastasis and the TNM staging. These results indicated that p-p70S6K may participate in the invasion and metastasis in the development of ESCC and downregulation of the expression of p-p70S6K could improve the sensitivity of cells to rapamycin in ESCC.http://dx.doi.org/10.1155/2016/7828916
spellingShingle Zhaoming Lu
Kezheng Peng
Ning Wang
Hong-Min Liu
Guiqin Hou
Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell Carcinoma
Journal of Immunology Research
title Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell Carcinoma
title_full Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell Carcinoma
title_fullStr Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell Carcinoma
title_full_unstemmed Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell Carcinoma
title_short Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell Carcinoma
title_sort downregulation of p70s6k enhances cell sensitivity to rapamycin in esophageal squamous cell carcinoma
url http://dx.doi.org/10.1155/2016/7828916
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AT ningwang downregulationofp70s6kenhancescellsensitivitytorapamycininesophagealsquamouscellcarcinoma
AT hongminliu downregulationofp70s6kenhancescellsensitivitytorapamycininesophagealsquamouscellcarcinoma
AT guiqinhou downregulationofp70s6kenhancescellsensitivitytorapamycininesophagealsquamouscellcarcinoma