PS-B01-9: APATINIB THROUGH ACTIVATING THE RHOA/ROCK SIGNALING PATHWAY TO CAUSE DYSFUNCTION OF VASCULAR SMOOTH MUSCLE CELLS

Abstract

Apatinib is a small molecule TKI that highly selectively binds to and strongly inhibits VEGFR2. Previous studies have shown that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. However, hypertension is one of the main adverse effects of antiangiogenic tumour drugs and affecting the application of the drugs. Previous studies have confirmed that the RhoA/ROCK pathway is involved in the pathogenesis of hypertension. Abnormal cell proliferation and invasion of vascular smooth muscle cells are among the primary causes of cardiovascular disease. In this study, an in vitro experiment was conducted to observe whether apatinib caused dysfunction of MOVAS cells through the RhoA/ROCK signalling pathway and whether it could be improved after Y27632 intervention. Subsequently, cell lines in which the LARG gene, which is involved in the RhoA/ROCK pathway, was knocked out were constructed to observe whether LARG knockdown could improve the proliferation, antiapoptosis, oxidative stress and mitochondrial autophagy of apatinib induced MOVAS cells. To provide a basis for the prevention and treatment of this type of hypertension.