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Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth

Loss or dysfunction of tumor suppressor retinoblastoma (RB) is a common feature in various tumors, and contributes to cancer cell stemness and drug resistance to cancer therapy. However, the strategy to suppress or eliminate Rb-deficient tumor cells remains unclear. In the present study, we accident...

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Autores principales: Li, Juan, Liu, Jie, Liang, Zheyong, He, Fang, Yang, Lu, Li, Pingping, Jiang, Yina, Wang, Bo, Zhou, Can, Wang, Yaochun, Ren, Yu, Yang, Jin, Zhang, Jianmin, Luo, Zhijun, Vaziri, Cyrus, Liu, Peijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386551/
https://www.ncbi.nlm.nih.gov/pubmed/28300827
http://dx.doi.org/10.1038/cddis.2017.46
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author Li, Juan
Liu, Jie
Liang, Zheyong
He, Fang
Yang, Lu
Li, Pingping
Jiang, Yina
Wang, Bo
Zhou, Can
Wang, Yaochun
Ren, Yu
Yang, Jin
Zhang, Jianmin
Luo, Zhijun
Vaziri, Cyrus
Liu, Peijun
author_facet Li, Juan
Liu, Jie
Liang, Zheyong
He, Fang
Yang, Lu
Li, Pingping
Jiang, Yina
Wang, Bo
Zhou, Can
Wang, Yaochun
Ren, Yu
Yang, Jin
Zhang, Jianmin
Luo, Zhijun
Vaziri, Cyrus
Liu, Peijun
author_sort Li, Juan
collection PubMed
description Loss or dysfunction of tumor suppressor retinoblastoma (RB) is a common feature in various tumors, and contributes to cancer cell stemness and drug resistance to cancer therapy. However, the strategy to suppress or eliminate Rb-deficient tumor cells remains unclear. In the present study, we accidentally found that reduction of DNA replication licensing factor MCM7 induced more apoptosis in RB-deficient tumor cells than in control tumor cells. Moreover, after a drug screening and further studies, we demonstrated that statin drug Simvastatin and Atorvastatin were able to inhibit MCM7 and RB expressions. Further study showed that Simvastatin and Atorvastatin induced more chromosome breaks and gaps of Rb-deficient tumor cells than control tumor cells. In vivo results showed that Simvastatin and Atorvastatin significantly suppressed Rb-deficient tumor growth than control in xenograft mouse models. The present work demonstrates that ‘old' lipid-lowering drugs statins are novel weapons against RB-deficient tumors due to their effects on suppressing MCM7 protein levels.
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spelling pubmed-53865512017-04-27 Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth Li, Juan Liu, Jie Liang, Zheyong He, Fang Yang, Lu Li, Pingping Jiang, Yina Wang, Bo Zhou, Can Wang, Yaochun Ren, Yu Yang, Jin Zhang, Jianmin Luo, Zhijun Vaziri, Cyrus Liu, Peijun Cell Death Dis Original Article Loss or dysfunction of tumor suppressor retinoblastoma (RB) is a common feature in various tumors, and contributes to cancer cell stemness and drug resistance to cancer therapy. However, the strategy to suppress or eliminate Rb-deficient tumor cells remains unclear. In the present study, we accidentally found that reduction of DNA replication licensing factor MCM7 induced more apoptosis in RB-deficient tumor cells than in control tumor cells. Moreover, after a drug screening and further studies, we demonstrated that statin drug Simvastatin and Atorvastatin were able to inhibit MCM7 and RB expressions. Further study showed that Simvastatin and Atorvastatin induced more chromosome breaks and gaps of Rb-deficient tumor cells than control tumor cells. In vivo results showed that Simvastatin and Atorvastatin significantly suppressed Rb-deficient tumor growth than control in xenograft mouse models. The present work demonstrates that ‘old' lipid-lowering drugs statins are novel weapons against RB-deficient tumors due to their effects on suppressing MCM7 protein levels. Nature Publishing Group 2017-03 2017-03-16 /pmc/articles/PMC5386551/ /pubmed/28300827 http://dx.doi.org/10.1038/cddis.2017.46 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Li, Juan
Liu, Jie
Liang, Zheyong
He, Fang
Yang, Lu
Li, Pingping
Jiang, Yina
Wang, Bo
Zhou, Can
Wang, Yaochun
Ren, Yu
Yang, Jin
Zhang, Jianmin
Luo, Zhijun
Vaziri, Cyrus
Liu, Peijun
Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth
title Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth
title_full Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth
title_fullStr Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth
title_full_unstemmed Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth
title_short Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth
title_sort simvastatin and atorvastatin inhibit dna replication licensing factor mcm7 and effectively suppress rb-deficient tumors growth
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386551/
https://www.ncbi.nlm.nih.gov/pubmed/28300827
http://dx.doi.org/10.1038/cddis.2017.46
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