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

doi:10.3892/ol.2018.9474

Low dose dinaciclib enhances doxorubicin‑induced senescence in myeloma RPMI8226 cells by transformation of the p21 and p16 pathways

Authors:
- Hailong Tang
- Li Xu
- Xue Liang
- Guangxun Gao
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Affiliations: Department of Hematology, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, P.R. China, School of Basic Medicine, Air Force Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: September 20, 2018 https://doi.org/10.3892/ol.2018.9474
Pages: 6608-6614
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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