Affiliation:
1. Department of Pathology, Nantong Tumor Hospital, Nantong, Jiangsu, China
2. Department of Pathology, Nantong Tumor Hospital, 30 North Tongyang Road, Pingchao, Nantong, Jiangsu, 226361, China
Abstract
Background and Purpose:
Breast cancer is one of the leading causes of cancer deaths in female
worldwide. Doxorubicin represents the most common chemotherapy for breast cancer, whereas side effects and
development of resistance impede its effect on chemotherapy. Nicotinamide (NAM), serves as the sirtuins’
inhibitor, effectively suppressing various types of cancer. However, the effects of NAM on drug resistance of
breast cancer are 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 while cell apoptosis was measured by TUNEL analysis. Expression
levels of SIRT1, phosphate Akt (P-Akt, Ser-473) and Akt were measured using western blot analysis. The interrelation
between SIRT1 and Akt was investigated by co-immunoprecipitation assay.
Results:
Treatment of nicotinamide combined with doxorubicin effectively inhibited cell growth, suppressed
cell migration, and promoted cell apoptosis of MCF7/ADR cells. Mechanistically, nicotinamide translocated
SIRT1 from the cell nucleus to cytoplasm, dissociated the connection between SIRT1 and Akt, and consequently
decreased expressions of SIRT1, and P-Akt, thereby inhibiting the growth of MCF7/ADR cells.
Conclusion:
Our results suggested that the value of nicotinamide is a potential therapeutic agent for breast
cancer treatment through downregulating SIRT1/Akt pathway, leading to the valid management of breast cancer
patients.
Funder
Technology Projects of Nantong
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Cited by
16 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献