Metformin exerts synergistic anti-proliferative effects with Liraglutide in human umbilical vein endothelial cells (HUVECs)

Document Type : Original Article


1 Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran

3 Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran

4 Pharmaceutical Sciences Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran Iran

5 Department of Pharmaceutics, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran



Objective(s): Metformin (Met) and Liraglutide (Lira) have been approved to treat type 2 diabetes mellitus and have cardioprotective effects. 
Materials and Methods: Human umbilical vein endothelial cells (HUVECs) were incubated with Met, Lira, or their combination in this study. 
Results: Results showed that the synergistic inhibitory effect of the two drugs on HUVECs proliferation was significant (75%) after 48 hr drug exposure. In addition, either Lira or Met alone had a marked tendency to inhibit the migration of HUVECs (42% and 39%). Almost a complete inhibition (97%) was demonstrated in combinational use after 48 hr treatment. After combining these two drugs, the apoptosis rate raised to 68%, which was a significant approval of synergistic apoptosis induction of Met and Lira. The combinational group indicated a substantial increase in VEGF, PDGF, and MMP-9 at 24 hr compared with the control. 
Conclusion: This study showed that combination therapy with Lira and Met could effectively reduce cell proliferation, induce apoptosis, and inhibit cell migration in the HUVECs. This study provides evidence to support using Met in combination with Lira as a treatment option for patients with type-2 diabetes and cancer.


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