Gefitinib-coated balloon inhibits the excessive hyperplasia of intima after vascular injuries through PI3K/AKT pathway.

Abstract

OBJECTIVE: To explore the effect of gefitinib-coated balloon suppressive action on the excessive hyperplasia of intima after balloon injury of common carotid artery in rats and on the PI3K/AKT signal pathway.METHODS: MTT method and the expression of Bcl-2 and Caspase-3 proteins were detected in vitro; Adult SD rats were randomly split into 5 groups, namely sham group, model group, low-dosage gefitinib-coated balloon group, high-dosage gefitinib-coated balloon group, and paclitaxel-coated balloon group. The intimal proliferation of arteries, PCNA, P-AKT and PI3K protein expression, the cell apoptosis, expression of MMP9, TGF and IL6 mRNA were measured by hematoxylin and eosin (H&E) staining, immunohistochemistry, TUNEL staining, and RT-qPCR.RESULTS: At the same time and concentration, Gefitinib suppressed the proliferation of smooth muscle cell more significantly than paclitaxel. Bcl-2 and Caspase-3 in vascular smooth muscle and endothelial cells (VSMC, EC) were significantly down-regulated and up-regulated after the cells were treated with gefitinib and paclitaxel. In gefitinib- and paclitaxel-coated balloon groups, significant up-regulations were found in the area of lumen. Furthermore, the expression of PCNA suggested that all coated balloons could suppress the excessive proliferation of smooth muscle cells in the hyperplastic intima compared with the control group. In gefitinib- and paclitaxel-coated balloon group, the expression of PI3K/AKT was significantly down-regulated. The use of drug-coated balloons mitigated the cell apoptosis in TUNEL. The expressions of MMP9, TGF and IL6 mRNA in the model group were obviously up-regulated; and they were obviously down-regulated in the high-dose gefitinib-coated balloon group compared with the model group.CONCLUSIONS: Gefitinib-coated balloons were able to suppress the excessive proliferation in the common carotid arterial intima of rats more effectively than the paclitaxel-coated ones. The underlying mechanism may cover the PI3K/AKT signal pathway.