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Oncotarget. 2019 Nov 5;10(60):6432-6443. doi: 10.18632/oncotarget.27266. eCollection 2019 Nov 5.

The anti-cancer effects of phenformin in thyroid cancer cell lines and in normal thyrocytes.

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Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy.
PHD course in Experimental Medicine, University of Pavia, Pavia, Italy.
Molecular Cardiology, ICS-Maugeri, Pavia, Italy.
Department of Biopharmaceutics and Clinical Pharmacy, The University of Jordan, Amman, Jordan.
Department of General and Minimally Invasive Surgery, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.


Phenformin is a biguanide drug which, besides the original anti-diabetic effect, also exerts anti-cancer effects. The aim of this study was to further characterize these latter in terms of both cell-viability and modulation of the secretion of the pro-tumorigenic chemokine CXCL8. Normal human thyrocytes in primary cultures (NHT) and thyroid cancer cell lines, TPC-1 and 8505C (RET/PTC and BRAFV600E mutated, respectively) were treated with increasing concentrations of phenformin at different times. Cell-viability was assessed by WST-1 and further characterized by AnnexinV/PI staining and cell proliferation colony-assay. CXCL8 levels were measured in cell supernatants. Phenformin reduced cell-viability in TPC-1 and 8505C and their ability to form colonies. In NHT cells, phenformin affected cell-viability only at the maximal dose but interestingly it inhibited CXCL8 secretion at all the concentrations not affecting cell-viability. Phenformin had no effect on CXCL8 secretion in thyroid cancer cell lines. Thus, phenformin exerts anti-cancer effects on both cancer cells (cell death induction) and surrounding normal cells (inhibition of CXCL8 secretion). These results highlight that the anti-cancer effects of phenformin are multifaceted and effective on both solid and soluble components of the tumor-microenvironment.


CXCL8; phenformin; thyroid cancer; tumor-microenvironment

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