Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma
The present study was performed to explore the effects of Notch pathway inhibition on the proliferation and apoptosis of renal carcinoma cells. The expression levels of Notch1 and Jagged1 were examined by western blot analysis and immunohistochemistry in pathologically identified clear cell renal ce...
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| Format: | Online |
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D.A. Spandidos
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063651/ |
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pubmed-40636512014-06-23 Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma WU, KERONG ZHANG, LI LIN, YIWEI YANG, KAI CHENG, YUE Articles The present study was performed to explore the effects of Notch pathway inhibition on the proliferation and apoptosis of renal carcinoma cells. The expression levels of Notch1 and Jagged1 were examined by western blot analysis and immunohistochemistry in pathologically identified clear cell renal cell carcinoma (RCC) and normal kidney tissues. Next, γ-secretase inhibitor was used to suppress the Notch pathway in renal carcinoma cell lines. The proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry analysis was performed to determine the apoptosis, as well as cell cycle alteration. The expression of Notch1 and Jagged1 proteins was detected to be higher in tumor tissues than in non-neoplastic tissues by western blot analysis. The positive staining rates of Notch1 and Jagged1 in clear cell RCC were higher than in normal kidney tissues [95.3 vs. 36.4% (P<0. 05); 93.0 vs. 42.4% (P<0.05), respectively]. The expression levels of Notch1 and Jagged1 were found to statistically correlate with tumor size, grade, TNM stage and disease relapse. The suppression of the Notch pathway was associated with cell proliferation inhibition, as well as induced G2/M phase cell cycle arrest and cell apoptosis. The Notch pathway may be important in oncogenesis of clear cell RCC and the γ-secretase inhibitor may be a potential agent for target therapy of RCC. D.A. Spandidos 2014-07 2014-04-22 /pmc/articles/PMC4063651/ /pubmed/24959218 http://dx.doi.org/10.3892/ol.2014.2078 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
WU, KERONG ZHANG, LI LIN, YIWEI YANG, KAI CHENG, YUE |
| spellingShingle |
WU, KERONG ZHANG, LI LIN, YIWEI YANG, KAI CHENG, YUE Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma |
| author_facet |
WU, KERONG ZHANG, LI LIN, YIWEI YANG, KAI CHENG, YUE |
| author_sort |
WU, KERONG |
| title |
Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma |
| title_short |
Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma |
| title_full |
Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma |
| title_fullStr |
Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma |
| title_full_unstemmed |
Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma |
| title_sort |
inhibition of γ-secretase induces g2/m arrest and triggers apoptosis in renal cell carcinoma |
| description |
The present study was performed to explore the effects of Notch pathway inhibition on the proliferation and apoptosis of renal carcinoma cells. The expression levels of Notch1 and Jagged1 were examined by western blot analysis and immunohistochemistry in pathologically identified clear cell renal cell carcinoma (RCC) and normal kidney tissues. Next, γ-secretase inhibitor was used to suppress the Notch pathway in renal carcinoma cell lines. The proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry analysis was performed to determine the apoptosis, as well as cell cycle alteration. The expression of Notch1 and Jagged1 proteins was detected to be higher in tumor tissues than in non-neoplastic tissues by western blot analysis. The positive staining rates of Notch1 and Jagged1 in clear cell RCC were higher than in normal kidney tissues [95.3 vs. 36.4% (P<0. 05); 93.0 vs. 42.4% (P<0.05), respectively]. The expression levels of Notch1 and Jagged1 were found to statistically correlate with tumor size, grade, TNM stage and disease relapse. The suppression of the Notch pathway was associated with cell proliferation inhibition, as well as induced G2/M phase cell cycle arrest and cell apoptosis. The Notch pathway may be important in oncogenesis of clear cell RCC and the γ-secretase inhibitor may be a potential agent for target therapy of RCC. |
| publisher |
D.A. Spandidos |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063651/ |
| _version_ |
1612103687467958272 |