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Low dose dinaciclib enhances doxorubicin-induced senescence in myeloma RPMI8226 cells by transformation of the p21 and p16 pathways
Multiple myeloma (MM) is a hematological malignancy that lacks a cure. However, novel combination therapy is a current anti-MM strategy. Doxorubicin (DOX) is a type of anthracycline which is a first-line chemotherapeutic for treating MM and induces senescence in many types of cancer. Dinaciclib is a...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202540/ https://www.ncbi.nlm.nih.gov/pubmed/30405800 http://dx.doi.org/10.3892/ol.2018.9474 |
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author | Tang, Hailong Xu, Li Liang, Xue Gao, Guangxun |
author_facet | Tang, Hailong Xu, Li Liang, Xue Gao, Guangxun |
author_sort | Tang, Hailong |
collection | PubMed |
description | Multiple myeloma (MM) is a hematological malignancy that lacks a cure. However, novel combination therapy is a current anti-MM strategy. Doxorubicin (DOX) is a type of anthracycline which is a first-line chemotherapeutic for treating MM and induces senescence in many types of cancer. Dinaciclib is a potent, small molecule CDK inhibitor with promise for treating several types of cancer in I/II phase clinical trials. In the present study the anticancer effects and underlying mechanisms of dinaciclib combined with DOX in MM RPMI-8226 cells were investigated. Results indicated that DOX induced cell viability inhibition, cell cycle arrest and senescence. Furthermore, DOX resulted in increased alterations in DNA damage-related proteins such as p-ATM, p-Chk2, p-p53, p21 and γH2AX, but not p16. Notably, the combination of dinaciclib and DOX inhibited cell growth and promoted senescence by transforming the suppressive effects of the ATM/Chk2/p53/p21 signaling pathway and enhancing the p16 signaling pathway. Thus, low-dose dinaciclib enhanced anti-MM effects mediated by DOX via transformation of p21-p16 signaling pathways, leading to accelerated senescence, but not apoptosis. The present findings suggest this approach may be a promising therapeutic strategy for the treatment of MM. |
format | Online Article Text |
id | pubmed-6202540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-62025402018-11-07 Low dose dinaciclib enhances doxorubicin-induced senescence in myeloma RPMI8226 cells by transformation of the p21 and p16 pathways Tang, Hailong Xu, Li Liang, Xue Gao, Guangxun Oncol Lett Articles Multiple myeloma (MM) is a hematological malignancy that lacks a cure. However, novel combination therapy is a current anti-MM strategy. Doxorubicin (DOX) is a type of anthracycline which is a first-line chemotherapeutic for treating MM and induces senescence in many types of cancer. Dinaciclib is a potent, small molecule CDK inhibitor with promise for treating several types of cancer in I/II phase clinical trials. In the present study the anticancer effects and underlying mechanisms of dinaciclib combined with DOX in MM RPMI-8226 cells were investigated. Results indicated that DOX induced cell viability inhibition, cell cycle arrest and senescence. Furthermore, DOX resulted in increased alterations in DNA damage-related proteins such as p-ATM, p-Chk2, p-p53, p21 and γH2AX, but not p16. Notably, the combination of dinaciclib and DOX inhibited cell growth and promoted senescence by transforming the suppressive effects of the ATM/Chk2/p53/p21 signaling pathway and enhancing the p16 signaling pathway. Thus, low-dose dinaciclib enhanced anti-MM effects mediated by DOX via transformation of p21-p16 signaling pathways, leading to accelerated senescence, but not apoptosis. The present findings suggest this approach may be a promising therapeutic strategy for the treatment of MM. D.A. Spandidos 2018-11 2018-09-20 /pmc/articles/PMC6202540/ /pubmed/30405800 http://dx.doi.org/10.3892/ol.2018.9474 Text en Copyright: © Tang 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 Tang, Hailong Xu, Li Liang, Xue Gao, Guangxun Low dose dinaciclib enhances doxorubicin-induced senescence in myeloma RPMI8226 cells by transformation of the p21 and p16 pathways |
title | Low dose dinaciclib enhances doxorubicin-induced senescence in myeloma RPMI8226 cells by transformation of the p21 and p16 pathways |
title_full | Low dose dinaciclib enhances doxorubicin-induced senescence in myeloma RPMI8226 cells by transformation of the p21 and p16 pathways |
title_fullStr | Low dose dinaciclib enhances doxorubicin-induced senescence in myeloma RPMI8226 cells by transformation of the p21 and p16 pathways |
title_full_unstemmed | Low dose dinaciclib enhances doxorubicin-induced senescence in myeloma RPMI8226 cells by transformation of the p21 and p16 pathways |
title_short | Low dose dinaciclib enhances doxorubicin-induced senescence in myeloma RPMI8226 cells by transformation of the p21 and p16 pathways |
title_sort | low dose dinaciclib enhances doxorubicin-induced senescence in myeloma rpmi8226 cells by transformation of the p21 and p16 pathways |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202540/ https://www.ncbi.nlm.nih.gov/pubmed/30405800 http://dx.doi.org/10.3892/ol.2018.9474 |
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