Metformin inhibits small intestinal neuroendocrine tumor proliferation in vivo

#4036

Introduction: Small intestinal neuroendocrine tumors (SI-NETs) are rare and slow-growing, with most patients being diagnosed at a late stage with distant metastases. Metformin has been hypothesized as a potential anti-tumor agent by several studies in the past few years. This has been further confirmed by experimental studies in which metformin has inhibited cancer cell growth in different cancers, and we recently demonstrated that metformin treatment repressed the cell viability of SI-NET cells and inhibited the proliferation of cell spheroids.

Aim(s): To investigate the effect of metformin on the proliferation of SI-NETs in vivo, identify novel molecular targets, and unravel mechanisms responsible for the anti-tumor activity of metformin.

Materials and methods: A SI-NET xenograft mouse model using SI-NET cell lines has been established in our research group for functional genomics in vivo studies. Xenografted mice were treated with metformin and a negative control for 28 days and then euthanized for tumor dissection. Dissected tumors were sectioned and subjected to tumor proliferation investigation by Ki-67 staining; caspase-3 expression for signs of apoptosis induction; and total RNA-seq and miRNA-seq for expression analysis.

Conference:

Presenting Author:

Authors: Axling F, Hellman P, Norlén O, Stålberg P, Barazeghi E,

Keywords: neuroendocrine neoplasm, SI-NET, in vivo model, metformin, RNA-seq, miRNA-seq, xenograft,