Shadboorestan Amir, Eftekhari Samane, Mottaghi-Dastjerdi Negar, Shahparvari Rezvan, Tarighi Parastoo, Jahandar Hoda, Faghihi Homa, Montazeri Hamed
Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
These authors contributed equally to this work.
Iran J Basic Med Sci. 2022 Apr;25(4):506-513. doi: 10.22038/IJBMS.2022.64117.14117.
Metformin (Met) and liraglutide (Lira) have been approved to treat type 2 diabetes mellitus and have cardioprotective effects.
Human umbilical vein endothelial cells (HUVECs) were incubated with Met, Lira, or their combination in this study.
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.
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.
二甲双胍(Met)和利拉鲁肽(Lira)已被批准用于治疗2型糖尿病,且具有心脏保护作用。
在本研究中,将人脐静脉内皮细胞(HUVECs)与二甲双胍、利拉鲁肽或它们的组合一起孵育。
结果显示,在药物暴露48小时后,两种药物对HUVECs增殖的协同抑制作用显著(75%)。此外,单独使用利拉鲁肽或二甲双胍均有明显的抑制HUVECs迁移的趋势(分别为42%和39%)。在48小时处理后,联合使用时几乎完全抑制(97%)。将这两种药物联合使用后,细胞凋亡率提高到68%,这显著证明了二甲双胍和利拉鲁肽协同诱导细胞凋亡。与对照组相比,联合用药组在24小时时VEGF、PDGF和MMP - 9显著增加。
本研究表明,利拉鲁肽和二甲双胍联合治疗可有效降低HUVECs中的细胞增殖、诱导细胞凋亡并抑制细胞迁移。本研究为支持将二甲双胍与利拉鲁肽联合作为2型糖尿病和癌症患者的治疗选择提供了证据。