The effect of Icaritin on airway smooth muscle cells proliferation and apoptosis

Abstract

Introduction: Airway smooth muscle cells (ASMCs) hyperplasia contributes to airway remodeling in asthma and is mainly caused by cell overgrowth and in-sufficient apoptosis. Icaritin, derived from Epimedium Flavonoids (EFs) could regulate many kinds of cell proliferation and apoptosis, but whether it acts on ASMCs proliferation and apoptosis, still unclear. Aims: To find out whether Icaritin could suppress proliferation while induce apoptosis of ASMCs. Methods: Rat ASMCs was isolated and used in this study. CKK-8 assay was performed for cell proliferation, flow cytometry was used to evaluate cell cycles and apoptosis, RT-PCR and Western blotting was used to detect mRNA and protein expression. Results: Icaritin inhibited rat ASMCs proliferation When treated with Icaritin, ASMCs proliferation was inhibited in dose-and time-dependent manner. The inhibitory effect increased largely from 40 μM to 70 μM. Cells in G0/G1-phase decreased but in S-phase increased dose dependently, and the expression of cyclin E increased but cyclin A decreased. These results indicated Icaritin inhibited ASMCs proliferation by inducing S-phase arrest. Icaritin induced rat ASMCs apoptosis When Icaritin was added with a series concentrations, it was found apoptotic cells dose dependently increased, activated caspase-8, caspase-3 and FADD expressions increased, indicating FADD/Caspase-8/Caspase-3 signal pathway may involve in Icaritin induced ASMCs apoptosis. Conclusions: We conclude Icaritin inhibites proliferation but induces apoptosis of rat ASMCs, this finding implys its potential application in asthma modeling intervention. But the detail mechanism needs to be further explored.