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Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma

Notch 1 is a key component of the Notch pathway, which performs a crucial role in clear cell renal cell carcinoma (CCRCC) development. The present study aimed to investigate whether Notch 1 could serve as a potential target for CCRCC treatment. Firstly, an association analysis was performed using 52...

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Autores principales: Zhuang, Zhiming, Lin, Jiangui, Huang, Yiqun, Lin, Tianqi, Zheng, Zhouda, Ma, Xudong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587946/
https://www.ncbi.nlm.nih.gov/pubmed/28927098
http://dx.doi.org/10.3892/ol.2017.6587
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author Zhuang, Zhiming
Lin, Jiangui
Huang, Yiqun
Lin, Tianqi
Zheng, Zhouda
Ma, Xudong
author_facet Zhuang, Zhiming
Lin, Jiangui
Huang, Yiqun
Lin, Tianqi
Zheng, Zhouda
Ma, Xudong
author_sort Zhuang, Zhiming
collection PubMed
description Notch 1 is a key component of the Notch pathway, which performs a crucial role in clear cell renal cell carcinoma (CCRCC) development. The present study aimed to investigate whether Notch 1 could serve as a potential target for CCRCC treatment. Firstly, an association analysis was performed using 52 CCRCC cases and 30 normal controls. The results indicated that Notch 1 protein expression in renal tissues was closely associated with the incidence of CCRCC. In addition, higher Notch 1 expression in CCRCC tissues was positively associated with higher tumor-node-metastasis stage and Fuhrman grade, in addition to larger tumor size. Subsequently, an in vitro study was conducted to examine the biological functions of Notch 1 in CCRCC 786-O cells through inhibiting the Notch 1 expression with Notch 1-specific small interfering RNA (siRNA). As a result, the inhibition of Notch 1 expression by increasing concentrations of Notch 1-specific siRNA dose-dependently decreased cell proliferation and increased cell apoptosis in 786-O cells. Furthermore, B-cell lymphoma-2 and procaspase-3 expression exhibited a dose-dependent decrease accompanied with a dose-dependent inactivation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway in Notch 1 siRNA-treated 786-O cells. These findings demonstrated that Notch 1 was associated with CCRCC carcinogenesis and progression, the underlying mechanism of which was that Notch 1 acted as an activator for cell proliferation and a suppressor for cell apoptosis through the Akt/mTOR signaling-dependent pathway in CCRCC. In conclusion, the present study confirmed that Notch 1 is a valuable target against cell survival and proliferation in CCRCC treatment.
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spelling pubmed-55879462017-09-18 Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma Zhuang, Zhiming Lin, Jiangui Huang, Yiqun Lin, Tianqi Zheng, Zhouda Ma, Xudong Oncol Lett Articles Notch 1 is a key component of the Notch pathway, which performs a crucial role in clear cell renal cell carcinoma (CCRCC) development. The present study aimed to investigate whether Notch 1 could serve as a potential target for CCRCC treatment. Firstly, an association analysis was performed using 52 CCRCC cases and 30 normal controls. The results indicated that Notch 1 protein expression in renal tissues was closely associated with the incidence of CCRCC. In addition, higher Notch 1 expression in CCRCC tissues was positively associated with higher tumor-node-metastasis stage and Fuhrman grade, in addition to larger tumor size. Subsequently, an in vitro study was conducted to examine the biological functions of Notch 1 in CCRCC 786-O cells through inhibiting the Notch 1 expression with Notch 1-specific small interfering RNA (siRNA). As a result, the inhibition of Notch 1 expression by increasing concentrations of Notch 1-specific siRNA dose-dependently decreased cell proliferation and increased cell apoptosis in 786-O cells. Furthermore, B-cell lymphoma-2 and procaspase-3 expression exhibited a dose-dependent decrease accompanied with a dose-dependent inactivation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway in Notch 1 siRNA-treated 786-O cells. These findings demonstrated that Notch 1 was associated with CCRCC carcinogenesis and progression, the underlying mechanism of which was that Notch 1 acted as an activator for cell proliferation and a suppressor for cell apoptosis through the Akt/mTOR signaling-dependent pathway in CCRCC. In conclusion, the present study confirmed that Notch 1 is a valuable target against cell survival and proliferation in CCRCC treatment. D.A. Spandidos 2017-09 2017-07-15 /pmc/articles/PMC5587946/ /pubmed/28927098 http://dx.doi.org/10.3892/ol.2017.6587 Text en Copyright: © Zhuang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhuang, Zhiming
Lin, Jiangui
Huang, Yiqun
Lin, Tianqi
Zheng, Zhouda
Ma, Xudong
Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma
title Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma
title_full Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma
title_fullStr Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma
title_full_unstemmed Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma
title_short Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma
title_sort notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587946/
https://www.ncbi.nlm.nih.gov/pubmed/28927098
http://dx.doi.org/10.3892/ol.2017.6587
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