Metformin inhibition of neuroblastoma cell proliferation is differently modulated by cell differentiation induced by retinoic acid or overexpression of NDM29 non-coding RNA

Cancer Cell International

Aldo Pagano³  Tullio Florio¹  Ranieri Cancedda³  Roberto Würth²  Arianna Gigoni³  Delfina Costa³ 

[1] Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy;Internal Medicine (DIMI), University of Genova, Genova, Italy;IRCCS-AOU San Martino-IST, Genova, Italy

关键词: Anti-cancer therapy;    Differentiation;    NDM29 ncRNA;    Neuroblastoma;    Metformin;   

Others  :  1121684
DOI  :  10.1186/1475-2867-14-59

 received in 2014-02-25, accepted in 2014-06-04,  发布年份 2014

【 摘 要 】

Background

Metformin is a widely used oral hypoglycemizing agent recently proposed as potential anti-cancer drug. In this study we report the antiproliferative effect of metformin treatment in a high risk neuroblastoma cell model, focusing on possible effects associated to different levels of differentiation and/or tumor initiating potential.

Methods

Antiproliferative and cytotoxic effects of metformin were tested in human SKNBE2 and SH-SY5Y neuroblastoma cell lines and in SKNBE2 cells in which differentiation is induced by retinoic acid treatment or stable overexpression of NDM29 non-coding RNA, both conditions characterized by a neuron-like differentiated phenotype.

Results

We found that metformin significantly inhibits the proliferation of NB cells, an effect that correlates with the inhibition of Akt, while AMPK activity resulted unchanged. Notably, metformin effects were modulated in a different ways by differentiating stimuli, being abolished after retinoic acid treatment but potentiated by overexpression of NDM29.

Conclusion

These data suggest the efficacy of metformin as neuroblastoma anticancer agent, and support the requirement of further studies on the possible role of the differentiation status on the antiproliferative effects of this drug.

【 授权许可】

   
2014 Costa et al.; licensee BioMed Central Ltd.

【 图 表 】

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