Paclitaxel inhibits asthmatic airway remodeling by inhibiting airway smooth muscle hyperplasia in vitro and in vivo

<bold>Introduction:</bold> Airway smooth muscle cells (ASMCs) are important airway structural cells, and their physiological dysfunction caused by over-proliferation is one of the important reasons for airway remodeling in asthma. Therefore, the development of novel drugs to inhibit ASMCs proliferation is of great significance for asthma treatment. Paclitaxel exhibits outstanding biological activities in inhibiting cell proliferation. But the effects of Paclitaxel on ASMCs have not been reported yet. <bold>Aims:</bold> The purpose of this study was to determine that paclitaxel plays an anti-asthmatic role in airway remodeling by inhibiting ASMCs proliferation. <bold>Methods:</bold> ASMCs was isolated from rats for this study. CCK-8 and Edu experiments were used to detect cell viability and proliferation. Flow cytometry was used to evaluate cell cycle. qRT-PCR and western blotting were used to detect the expression of Cyclin-dependent kinase 1 (Cdk1). <bold>Results:</bold> Paclitaxel inhibits primary ASMCs proliferation. Paclitaxel induced ASMCs proliferation in a dose - and time-dependent manner. The significant inhibitory effect was in the range of 50 nM to 100 nM. Paclitaxel blocked cell cycle at G2/M phase with a dose-dependent manner and the blocking effect was nearly saturated at 100nM. Moreover, the expression of Cdk1 was decreased by paclitaxel treatment. An OVA-induced asthma model was established and treated with paclitaxel. HE staining found that paclitaxel has the ability to be a potential anti-asthma drug. <bold>Conclutions:</bold> Our study found that Paclitaxel could inhibit ASMCs proliferationin vitroand airway smooth muscle hyperplasia in vivo. But the mechanism needs to be further explored.