Nicotinamide Overcomes Doxorubicin Resistance of Breast Cancer Cells through Deregulating SIRT1/Akt Pathway

Author(s): Yingze Wei, Yan Guo, Jianyun Zhou, Kui Dai, Qiang Xu, Xiaoxia Jin*.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 19 , Issue 5 , 2019

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Abstract:

Background and Purpose: Breast cancer is one of the leading causes of cancer deaths in female worldwide. Doxorubicin represent the most common chemotherapy for breast cancer, whereas side effects and development of resistance impedes its effect of chemotherapy. Nicotinamide (NAM), served as the sirtuins’ inhibitor, effectively suppressed various types of cancer. However, the effects of NAM on drug resistance of breast cancer is need to be fully investigated.

Methods: Breast cancer doxorubicin-resistant cells MCF-7/ADR and doxorubicin-sensitive cells MCF-7 were applied in this study. Cell proliferation was assessed by CCK8 and colony-forming assays. Cell migration was evaluated by scratch test and transwell assay. Cell apoptosis was measured by TUNEL analysis. Expression levels of SIRT1, phosphated Akt (P-Akt, Ser-473) and Akt were measured using western blot analysis. Interrelation between SIRT1 and Akt was investigated by Co-Immunoprecipitation assay.

Results: Treatment of nicotinamide combined with doxorubicin effectively inhibited cell growth, supressed cell migration, and promoted cell apoptosis of MCF7/ADR cells. Mechanismly, nicotinamide translocated SIRT1 from cell nucleus to cytoplasm, dissociated the connection between SIRT1 and Akt, consequently decreased expressions of SIRT1, and P-Akt, thereby inhibited the growth of MCF7/ADR cells.

Conclusions: Our results suggested the value of nicotinamide as a potential therapeutic agent for breast cancer treatment through downregulating SIRT1/Akt pathway, leading to the valid management of breast cancer patients.

Keywords: Breast cancer, nicotinamide, doxorubicin resistance, SIRT1, Akt, P-Akt.

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Article Details

VOLUME: 19
ISSUE: 5
Year: 2019
Page: [687 - 696]
Pages: 10
DOI: 10.2174/1871520619666190114160457

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