Background: Larynx cancer (LCa) is the most common head and neck cancer and accounts
for 1-2.5% of all human cancers worldwide. Metformin, an oral anti-diabetic drug, has been recently
shown to have anti-cancer activity in various cancer types, and there are several studies in the literature
pointing to its potential to sensitize cancer cells to chemotherapeutic drugs.
Objective: This study was aimed at exploring the anti-cancer effects of metformin alone or in combination
with 5-fluorouracil (5-FU) on Hep-2 cells.
Methods: The effects of metformin and/or 5-FU on the proliferative, clonogenic, and apoptotic potential
of Hep-2 cells were evaluated with Cell Viability Detection Kit-8, soft agar assay and Annexin VFITC
Apoptosis assay, respectively. Migratory and invasive potential of cells was tested using
scratch, transwell migration and Matrigel invasion assays. Gene expression of cells exposed to metformin
and/or 5-FU was profiled using RT2 mRNA PCR Array plates.
Results: Treatment of Hep-2 cells with metformin inhibited cell proliferation by inducing apoptosis, and
suppressed cell migration. Besides, treatment of metformin along with 5-FU improved the antiproliferative
and anti-migratory effects of 5-FU. However, unexpectedly, metformin was found to enhance
cellular invasion and reverse the inhibitory effect of 5-FU on the invasive potential of Hep-2 cells.
Conclusion: Our findings suggest that metformin might be used as an adjuvant agent in the treatment
of LCa. However, the potential of metformin to promote the invasion of cancer cells should not be