Effect Of Arsenic Trioxide On Proliferation And Migration Of Cultured Rabbit Aortic Smooth Muscle Cells

Coronary artery stents have emerged as the preferred tool for percutaneous coronary interventions during the past two decades by eliminating abrupt vessel closure and reducing restenosis compared with balloon angioplasty. And is currently one of the most commonly used percutaneous coronary intervention in many countries. But restenosis is still the most important long-term limitation of stent implantation for coronary artery disease, occurring in 10-50% of patients. Therefore, how to reduce the ratio of in-stent restenosis (ISR) is challenges both vascular biologist and interventional cardiologist. Nowadays it was widely accepted that growth and migration of vascular smooth-muscle cells result in neointimal proliferation after vascular injury are the key mechanism of in-stent restenosis. The rationale of the most recent approaches to restenosis (e.g. antineoplastic and antiproliferation agents) arises from the similarity between tumors-cell growth and the benign tissue proliferation that characterizes intimal hyperplasia. This is therefore a fertile area for the development of therapeutics to inhibit intimal hyperplasia.Arsenic trioxide is a kind of traditional Chinese medicine. Althougharsenic can be poisonous, it also attribute to growth of human and animals. In recent years, scholars have demonstrated that arsenic trioxide could inhibit tumor cells proliferation and improve their apoptosis.Objective: 1 To study the effects of AS2O3 on the proliferation and migration of cultured rabbit vascular smooth muscle cells of thoracic aorta; 2 To probe into the mechanism of how does AS2O3 work.Methods: Vascular smooth muscle cells of rabbits were cultured in vitro, and the cells of 3-8 passages of cultured VSMC were used in the experiment and were divided into control group and AS2O3 group according to different concentrations of AS2O3. AS2O3 group was subdivided into seven groups by concentration. MTT assay, 3H-TdR and microscope were used respectively to observed the ratio of cell proliferation, synthesization of DNA and migration in comparison with the control group; Cell cycle analysis was performed by flow cytometry.Result: 1 the ratio of cell proliferation rate were inhibited in AS2O3 groups compared with the control group; 2 In AS2O3 groups the distance of VSMC migration were decrease in a dose-dependent manner as compared with the control group; 3 detected by flow cytometry, most of VSMCs were inhibited to through the restriction point of cell cycle and accumulated in G0/G1 compared with the control group(P<0.05).Conclusion: AS2O3 can significantly inhibit the vascular smooth muscle cell proliferation and migration in vitro. To inhibit VSMC through the restriction point of cell cycle, which result in accumulation of VSMC in G0/G1, are likely to the mechanism of its action.