Table 2.

Studies on metformin treatment to date in neuroblastoma.

Reference/s	Year	Study types	Cell lines/animal model	Effects
[30]	2014	In vitro	SKNBE2 and SH-SY5Y cell lines	Significant reduction in the proliferation rate and cell viability, due to inhibition of AKT phosphorylation, and an increased cell death, via apoptosis-independent pathways.
[31]	2014	In vivo	SH-SY5Y and SK-N-BE xenograft NB mouse models	Significant inhibition of tumor growth and NB cell viability, interfering with spheroid formation in 3D cultures. Modulation of Rho-GTPases and AMPK activation mediate metformin effects on NB cell survival.
[32]	2015	In vitro	SK-N-AS and CHP-212 cell lines	Inhibition of cell proliferation and induction of apoptosis.
[33]	2015	In vitro	SH-SY5Y cell line	Reduction of proliferation rate, viability, and invasive potential.