Apatinib treatment increases the expression of mitochondria-associated endoplasmic reticulum membranes proteins

Abstract Background Blood pressure elevation is a common adverse effect of tyrosine kinase inhibitors (TKIs). Mitochondria-associated endoplasmic reticulum membranes (MAMs) have been implicated in the onset and progression of cardiovascular diseases in recent years. However, the role of MAMs in TKI-induced blood pressure elevation remains unclear. This study aims to determine whether MAMs are involved in the process of TKI-induced blood pressure increase in gastric cancer mouse models. Methods Human gastric adenocarcinoma MKN-45 cells and Balb/c nude mice were used to establish gastric cancer models. Apatinib was administered by gavage at a dose of 50 mg/kg/day for 4 weeks, while the control group received an equivalent volume of normal saline. The expression of MAM-associated proteins in the aortic tissues of mice was evaluated using Western blot analysis. Results Compared to the control group, the apatinib-treated group exhibited significant increases in the expression of MAM-related proteins and pathways, including the tethering proteins IP3R1, VDAC1, FUNDC1, and MFN2 (P 0.05). Conclusion Apatinib treatment increases the expression of MAM-associated proteins, indicating that MAM activity is enhanced in the aortic tissue following apatinib intervention. However, the mechanisms linking MAMs to apatinib-induced blood pressure elevation warrant further investigation. Figure1